Pain management

From Wikipedia, the free encyclopedia

Opium poppies such as this one provide ingredients for the class of analgesics called opiates

 

Pain management, pain medicine, pain control or algiatry, is a branch of medicine employing an interdisciplinary approach for easing the suffering and improving the quality of life of those living with chronic pain The typical pain management team includes medical practitioners, pharmacists, clinical psychologists, physiotherapists, occupational therapists, physician assistants, nurses. The team may also include other mental health specialists and massage therapists. Pain sometimes resolves promptly once the underlying trauma or pathology has healed, and is treated by one practitioner, with drugs such as analgesics and (occasionally) anxiolytics. Effective management of chronic (long-term) pain, however, frequently requires the coordinated efforts of the management team.

Medicine treats injury and pathology to support and speed healing; and treats distressing symptoms such as pain to relieve suffering during treatment and healing. When a painful injury or pathology is resistant to treatment and persists, when pain persists after the injury or pathology has healed, and when medical science cannot identify the cause of pain, the task of medicine is to relieve suffering. Treatment approaches to chronic pain include pharmacological measures, such as analgesics, antidepressants and anticonvulsants, interventional procedures, physical therapy, physical exercise, application of ice and/or heat, and psychological measures, such as biofeedback and cognitive behavioral therapy.

Uses

Pain can have many causes and there are many possible treatments for it. In the nursing profession, one common definition of pain is any problem that is "whatever the experiencing person says it is, existing whenever the experiencing person says it does". Different sorts of pain management address different sorts of pain. 

Pain management includes patient communication about the pain problem. To define the pain problem, a health care provider will likely ask questions such as these:

• How intense is the pain?
• How does the pain feel?
• Where is the pain?
• What, if anything, makes the pain lessen?
• What, if anything, makes the pain increase?
• When did the pain start?

After asking questions such as these, the health care provider will have a description of the pain. Pain management will then be used to address that pain.

Adverse effects

There are many types of pain management, and each of them have their own benefits, drawbacks, and limits.

A common difficulty in pain management is communication. People experiencing pain may have difficulty recognizing or describing what they feel and how intense it is. Health care providers and patients may have difficulty communicating with each other about how pain responds to treatments. There is a continuing risk in many types of pain management for the patient to take treatment which is less effective than needed or which causes other difficulty and side effects. Some treatments for pain can be harmful if overused. A goal of pain management for the patient and their health care provider to identify the amount of treatment which addresses the pain but which is not too much treatment.

Another problem with pain management is that pain is the body's natural way of communicating a problem. Pain is supposed to resolve as the body heals itself with time and pain management. Sometimes pain management covers a problem, and the patient might be less aware that they need treatment for a deeper problem.

Physical approach

Physical medicine and rehabilitation

Physical medicine and rehabilitation employs diverse physical techniques such as thermal agents and electrotherapy, as well as therapeutic exercise and behavioral therapy, alone or in tandem with interventional techniques and conventional pharmacotherapy to treat pain, usually as part of an interdisciplinary or multidisciplinary program. The Center for Disease Control recommends that physical therapy and exercise can be prescribed as a positive alternative to opioids for decreasing one's pain in multiple injuries, illnesses, or diseases. This can include chronic low back pain, osteoarthritis of the hip and knee, or fibromyalgia. Exercise alone or with other rehabilitation disciplines (such as psychologically based approaches) can have a positive effect on reducing pain. In addition to improving pain, exercise also can improve one's well-being and general health.

Exercise interventions

Physical activity interventions, such as tai chi, yoga and Pilates, promote harmony of the mind and body through total body awareness. These ancient practices incorporate breathing techniques, meditation and a wide variety of movements, while training the body to perform functionally by increasing strength, flexibility, and range of motion. Physical activity and exercise may improve chronic pain (pain lasting more than 12 weeks), and overall quality of life, while minimizing the need for pain medications.

TENS

Transcutaneous electrical nerve stimulation has been found to be ineffective for lower back pain, however, it might help with diabetic neuropathy.

Acupuncture

Acupuncture involves the insertion and manipulation of needles into specific points on the body to relieve pain or for therapeutic purposes. An analysis of the 13 highest quality studies of pain treatment with acupuncture, published in January 2009 in the British Medical Journal, was unable to quantify the difference in the effect on pain of real, sham and no acupuncture.

Light therapy

Research has not found evidence that light therapy such as low level laser therapy is an effective therapy for relieving low back pain.

Interventional procedures

Interventional procedures - typically used for chronic back pain - include epidural steroid injections, facet joint injections, neurolytic blocks, spinal cord stimulators and intrathecal drug delivery system implants. 

Pulsed radiofrequency, neuromodulation, direct introduction of medication and nerve ablation may be used to target either the tissue structures and organ/systems responsible for persistent nociception or the nociceptors from the structures implicated as the source of chronic pain.

An intrathecal pump used to deliver very small quantities of medications directly to the spinal fluid. This is similar to epidural infusions used in labour and postoperatively. The major differences are that it is much more common for the drug to be delivered into the spinal fluid (intrathecal) rather than epidurally, and the pump can be fully implanted under the skin.

A spinal cord stimulator is an implantable medical device that creates electric impulses and applies them near the dorsal surface of the spinal cord provides a paresthesia ("tingling") sensation that alters the perception of pain by the patient.

Psychological approach

Cognitive behavioral therapy

Cognitive behavioral therapy (CBT) for pain helps patients with pain to understand the relationship between one's physiology (e.g., pain and muscle tension), thoughts, emotions, and behaviors. A main goal in treatment is cognitive restructuring to encourage helpful thought patterns, targeting a behavioral activation of healthy activities such as regular exercise and pacing. Lifestyle changes are also trained to improve sleep patterns and to develop better coping skills for pain and other stressors using various techniques (e.g., relaxation, diaphragmatic breathing, and even biofeedback). 

Studies have demonstrated the usefulness of cognitive behavioral therapy in the management of chronic low back pain, producing significant decreases in physical and psychosocial disability. CBT is significantly more effective than standard care in treatment of people with body-wide pain, like fibromyalgia. Evidence for the usefulness of CBT in the management of adult chronic pain is generally poorly understood, due partly to the proliferation of techniques of doubtful quality, and the poor quality of reporting in clinical trials. The crucial content of individual interventions has not been isolated and the important contextual elements, such as therapist training and development of treatment manuals, have not been determined. The widely varying nature of the resulting data makes useful systematic review and meta-analysis within the field very difficult.

In 2012, a systematic review of randomized controlled trials (RCTs) evaluated the clinical effectiveness of psychological therapies for the management of adult chronic pain (excluding headaches). There is no evidence that behaviour therapy (BT) is effective for reducing this type of pain, however BT may be useful for improving a persons mood immediately after treatment. This improvement appears to be small, and is short term in duration. CBT may have a small positive short-term effect on pain immediately following treatment. CBT may also have a small effect on reducing disability and potential catastrophizing that may be associated with adult chronic pain. These benefits do not appear to last very long following the therapy. CBT may contribute towards improving the mood of an adult who experiences chronic pain, and there is a possibility that this benefit may be maintained for longer periods of time.

For children and adolescents, a review of RCTs evaluating the effectiveness of psychological therapy for the management of chronic and recurrent pain found that psychological treatments are effective in reducing pain when people under 18 years old have headaches. This beneficial effect may be maintained for at least three months following the therapy. Psychological treatments may also improve pain control for children or adolescents who experience pain not related to headaches. It is not known if psychological therapy improves a child or adolescents mood and the potential for disability related to their chronic pain.

Hypnosis

A 2007 review of 13 studies found evidence for the efficacy of hypnosis in the reduction of pain in some conditions, though the number of patients enrolled in the studies was small, bringing up issues of power to detect group differences, and most lacked credible controls for placebo and/or expectation. The authors concluded that "although the findings provide support for the general applicability of hypnosis in the treatment of chronic pain, considerably more research will be needed to fully determine the effects of hypnosis for different chronic-pain conditions."

Hypnosis has reduced the pain of some noxious medical procedures in children and adolescents, and in clinical trials addressing other patient groups it has significantly reduced pain compared to no treatment or some other non-hypnotic interventions. However, no studies have compared hypnosis to a convincing placebo, so the pain reduction may be due to patient expectation (the "placebo effect"). The effects of self hypnosis on chronic pain are roughly comparable to those of progressive muscle relaxation.

Mindfulness meditation

A meta-analysis of studies that used techniques centered around the concept of mindfulness, concluded, "Findings suggest that MBIs decrease the intensity of pain for chronic pain patients."

Medications

The World Health Organization (WHO) recommends a pain ladder for managing analgesia. It was first described for use in cancer pain, but it can be used by medical professionals as a general principle when dealing with analgesia for any type of pain. In the treatment of chronic pain, whether due to malignant or benign processes, the three-step WHO Analgesic Ladder provides guidelines for selecting the kind and stepping up the amount of analgesia. The exact medications recommended will vary with the country and the individual treatment center, but the following gives an example of the WHO approach to treating chronic pain with medications. If, at any point, treatment fails to provide adequate pain relief, then the doctor and patient move onto the next step. 

Common types of pain and typical drug management
Pain type	typical initial drug treatment	comments
headache	paracetamol /acetaminophen, NSAIDs	doctor consultation is appropriate if headaches are severe, persistent, accompanied by fever, vomiting, or speech or balance problems; self-medication should be limited to two weeks
migraine	paracetamol, NSAIDs	triptans are used when the others do not work, or when migraines are frequent or severe
menstrual cramps	NSAIDs	some NSAIDs are marketed for cramps, but any NSAID would work
minor trauma, such as a bruise, abrasions, sprain	paracetamol, NSAIDs	opioids not recommended
severe trauma, such as a wound, burn, bone fracture, or severe sprain	opioids	more than two weeks of pain requiring opioid treatment is unusual
strain or pulled muscle	NSAIDs, muscle relaxants	if inflammation is involved, NSAIDs may work better; short-term use only
minor pain after surgery	paracetamol, NSAIDs	opioids rarely needed
severe pain after surgery	opioids	combinations of opioids may be prescribed if pain is severe
muscle ache	paracetamol, NSAIDs	if inflammation involved, NSAIDs may work better.
toothache or pain from dental procedures	paracetamol, NSAIDs	this should be short term use; opioids may be necessary for severe pain
kidney stone pain	paracetamol, NSAIDs, opioids	opioids usually needed if pain is severe.
pain due to heartburn or gastroesophageal reflux disease	antacid, H2 antagonist, proton-pump inhibitor	heartburn lasting more than a week requires medical attention; aspirin and NSAIDs should be avoided
chronic back pain	paracetamol, NSAIDs	opioids may be necessary if other drugs do not control pain and pain is persistent
osteoarthritis pain	paracetamol, NSAIDs	medical attention is recommended if pain persists.
fibromyalgia	antidepressant, anticonvulsant	evidence suggests that opioids are not effective in treating fibromyalgia

Mild pain

Paracetamol (acetaminophen), or a nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen.

Mild to moderate pain

Paracetamol, an NSAID and/or paracetamol in a combination product with a weak opioid such as tramadol, may provide greater relief than their separate use. Also a combination of opioid with acetaminophen can be frequently used such as Percocet, Vicodin, or Norco.

Moderate to severe pain

When treating moderate to severe pain, the type of the pain, acute or chronic, needs to be considered. The type of pain can result in different medications being prescribed. Certain medications may work better for acute pain, others for chronic pain, and some may work equally well on both. Acute pain medication is for rapid onset of pain such as from an inflicted trauma or to treat post-operative pain. Chronic pain medication is for alleviating long-lasting, ongoing pain. 

Morphine is the gold standard to which all narcotics are compared. Semi-synthetic derivatives of morphine such as hydromorphone (Dilaudid), oxymorphone (Numorphan, Opana), nicomorphine (Vilan), hydromorphinol and others vary in such ways as duration of action, side effect profile and milligramme potency. Fentanyl has the benefit of less histamine release and thus fewer side effects. It can also be administered via transdermal patch which is convenient for chronic pain management. In addition to the intrathecal patch and injectable Sublimaze, the FDA has approved various immediate release fentanyl products for breakthrough cancer pain (Actiq/OTFC/Fentora/Onsolis/Subsys/Lazanda/Abstral). Oxycodone is used across the Americas and Europe for relief of serious chronic pain; its main slow-release formula is known as OxyContin, and short-acting tablets, capsules, syrups and ampules are available making it suitable for acute intractable pain or breakthrough pain. Diamorphine, methadone and buprenorphine are used less frequently. Pethidine, known in North America as meperidine, is not recommended for pain management due to its low potency, short duration of action, and toxicity associated with repeated use. Pentazocine, dextromoramide and dipipanone are also not recommended in new patients except for acute pain where other analgesics are not tolerated or are inappropriate, for pharmacological and misuse-related reasons. In some countries potent synthetics such as piritramide and ketobemidone are used for severe pain, and tapentadol is a newer agent introduced in the last decade. 

For moderate pain, tramadol, codeine, dihydrocodeine, and hydrocodone are used, with nicocodeine, ethylmorphine and propoxyphene and dextropropoxyphene less commonly. 

Drugs of other types can be used to help opioids combat certain types of pain, for example, amitriptyline is prescribed for chronic muscular pain in the arms, legs, neck and lower back with an opiate, or sometimes without it and/or with an NSAID. 

While opiates are often used in the management of chronic pain, high doses are associated with an increased risk of opioid overdose.

Opioids

From the Food and Drug Administration's website: "According to the National Institutes of Health, studies have shown that properly managed medical use of opioid analgesic compounds (taken exactly as prescribed) is safe, can manage pain effectively, and rarely causes addiction."

Opioid medications can provide short, intermediate or long acting analgesia depending upon the specific properties of the medication and whether it is formulated as an extended release drug. Opioid medications may be administered orally, by injection, via nasal mucosa or oral mucosa, rectally, transdermally, intravenously, epidurally and intrathecally. In chronic pain conditions that are opioid responsive a combination of a long-acting (OxyContin, MS Contin, Opana ER, Exalgo and Methadone) or extended release medication is often prescribed in conjunction with a shorter-acting medication (oxycodone, morphine or hydromorphone) for breakthrough pain, or exacerbations. 

Most opioid treatment used by patients outside of healthcare settings is oral (tablet, capsule or liquid), but suppositories and skin patches can be prescribed. An opioid injection is rarely needed for patients with chronic pain. 

Although opioids are strong analgesics, they do not provide complete analgesia regardless of whether the pain is acute or chronic in origin. Opioids are efficacious analgesics in chronic malignant pain and modestly effective in nonmalignant pain management. However, there are associated adverse effects, especially during the commencement or change in dose. When opioids are used for prolonged periods drug tolerance, chemical dependency, diversion and addiction may occur.

Clinical guidelines for prescribing opioids for chronic pain have been issued by the American Pain Society and the American Academy of Pain Medicine. Included in these guidelines is the importance of assessing the patient for the risk of substance abuse, misuse, or addiction; a personal or family history of substance abuse is the strongest predictor of aberrant drug-taking behavior. Physicians who prescribe opioids should integrate this treatment with any psychotherapeutic intervention the patient may be receiving. The guidelines also recommend monitoring not only the pain but also the level of functioning and the achievement of therapeutic goals. The prescribing physician should be suspicious of abuse when a patient reports a reduction in pain but has no accompanying improvement in function or progress in achieving identified goals.

Commonly-used long-acting opioids and their parent compound:

• OxyContin (oxycodone)
• Hydromorph Contin (hydromorphone)
• MS Contin (morphine)
• M-Eslon (morphine)
• Exalgo (hydromorphone)
• Opana ER (oxymorphone)
• Duragesic (fentanyl)
• Nucynta ER (tapentadol)
• Metadol/Methadose (methadone)*
• Hysingla ER (hydrocodone bitartrate)
• Zohydro ER (hydrocodone bicarbonate)

*Methadone can be used for either treatment of opioid addiction/detoxification when taken once daily or as a pain medication usually administered on an every 12-hour or 8-hour dosing interval.

Nonsteroidal anti-inflammatory drugs

The other major group of analgesics are nonsteroidal anti-inflammatory drugs (NSAID). Acetaminophen/paracetamol is not always included in this class of medications. However, acetaminophen may be administered as a single medication or in combination with other analgesics (both NSAIDs and opioids). The alternatively prescribed NSAIDs such as ketoprofen and piroxicam have limited benefit in chronic pain disorders and with long-term use are associated with significant adverse effects. The use of selective NSAIDs designated as selective COX-2 inhibitors have significant cardiovascular and cerebrovascular risks which have limited their utilization.

Antidepressants and antiepileptic drugs

Some antidepressant and antiepileptic drugs are used in chronic pain management and act primarily within the pain pathways of the central nervous system, though peripheral mechanisms have been attributed as well. These mechanisms vary and in general are more effective in neuropathic pain disorders as well as complex regional pain syndrome.

Cannabinoids

Chronic pain is one of the most commonly cited reasons for the use of medical marijuana. A 2012 Canadian survey of participants in their medical marijuana program found that 84% of respondents reported using medical marijuana for the management of pain.

Evidence of medical marijuana's pain mitigating effects is generally conclusive. Detailed in a 1999 report by the Institute of Medicine, "the available evidence from animal and human studies indicates that cannabinoids can have a substantial analgesic effect". In a 2013 review study published in Fundamental & Clinical Pharmacology, various studies were cited in demonstrating that cannabinoids exhibit comparable effectiveness to opioids in models of acute pain and even greater effectiveness in models of chronic pain.

Other analgesics

Other drugs are often used to help analgesics combat various types of pain, and parts of the overall pain experience, and are hence called analgesic adjuvant medications. Gabapentin—an anti-epileptic—not only exerts effects alone on neuropathic pain, but can potentiate opiates. While perhaps not prescribed as such, other drugs such as Tagamet (cimetidine) and even simple grapefruit juice may also potentiate opiates, by inhibiting CYP450 enzymes in the liver, thereby slowing metabolism of the drug. In addition, orphenadrine, cyclobenzaprine, trazodone and other drugs with anticholinergic properties are useful in conjunction with opioids for neuropathic pain. Orphenadrine and cyclobenzaprine are also muscle relaxants, and therefore particularly useful in painful musculoskeletal conditions. Clonidine has found use as an analgesic for this same purpose, and all of the mentioned drugs potentiate the effects of opioids overall.

Society and culture

The medical treatment of pain as practiced in Greece and Turkey is called algology (from the Greek άλγος, algos, "pain"). The Hellenic Society of Algology and the Turkish Algology-Pain Society are the relevant local bodies affiliated to the International Association for the Study of Pain (IASP).

Undertreatment

Undertreatment of pain is the absence of pain management therapy for a person in pain when treatment is indicated. 

Consensus in evidence-based medicine and the recommendations of medical specialty organizations establish the guidelines which determine the treatment for pain which health care providers ought to offer. For various social reasons, persons in pain may not seek or may not be able to access treatment for their pain. The Joint Commission, which has long recognized nonpharmacological approaches to pain, emphasizes the importance of strategies needed to facilitate both access and coverage to nonpharmacological therapies. Users of nonpharmacological therapy providers for pain management generally have lower insurance expenditures than those who did not use them. At the same time, health care providers may not provide the treatment which authorities recommend. The need for an informed strategy including all evidence-based comprehensive pain care is demonstrated to be in the patients' best interest. Healthcare providers' failure to educate patients and recommend nonpharmacologic care should be considered unethical.

In children

Acute pain is common in children and adolescents as a result of injury, illness, or necessary medical procedures. Chronic pain is present in approximately 15–25% of children and adolescents, and may be caused by an underlying disease, such as sickle cell anemia, cystic fibrosis, rheumatoid arthritis, or cancer or by functional disorders such as migraines, fibromyalgia, or complex regional pain.

Assessment

Young children can indicate their level of pain by pointing to the appropriate face on a children's pain scale.

 

Pain assessment in children is often challenging due to limitations in developmental level, cognitive ability, or their previous pain experiences. Clinicians must observe physiological and behavioral cues exhibited by the child to make an assessment. Self-report, if possible, is the most accurate measure of pain; self-report pain scales developed for young children involve matching their pain intensity to photographs of other children's faces, such as the Oucher Scale, pointing to schematics of faces showing different pain levels, or pointing out the location of pain on a body outline. Questionnaires for older children and adolescents include the Varni-Thompson Pediatric Pain Questionnaire (PPQ) and the Children’s Comprehensive Pain Questionnaire, which are often utilized for individuals with chronic or persistent pain.

Nonpharmacologic

Caregivers may provide nonpharmacological treatment for children and adolescents because it carries minimal risk and is cost effective compared to pharmacological treatment. Nonpharmacologic interventions vary by age and developmental factors. Physical interventions to ease pain in infants include swaddling, rocking, or sucrose via a pacifier, whereas those for children and adolescents include hot or cold application, massage, or acupuncture. Cognitive behavioral therapy (CBT) aims to reduce the emotional distress and improve the daily functioning of school-aged children and adolescents with pain through focus on changing the relationship between their thoughts and emotions in addition to teaching them adaptive coping strategies. Integrated interventions in CBT include relaxation technique, mindfulness, biofeedback, and acceptance (in the case of chronic pain). Many therapists will hold sessions for caregivers to provide them with effective management strategies.

Pharmacologic

Acetaminophen, nonsteroidal anti-inflammatory agents, and opioid analgesics are commonly used to treat acute or chronic pain symptoms in children and adolescents, but a pediatrician should be consulted before administering any medication.

Professional certification

Pain management practitioners come from all fields of medicine. In addition to medical practitioners, a pain management team may often benefit from the input of pharmacists, physiotherapists, clinical psychologists and occupational therapists, among others. Together the multidisciplinary team can help create a package of care suitable to the patient. 

Pain physicians are often fellowship-trained board-certified anesthesiologists, neurologists, physiatrists or psychiatrists. Palliative care doctors are also specialists in pain management. The American Board of Anesthesiology, the American Osteopathic Board of Anesthesiology (recognized by the AOABOS), the American Board of Physical Medicine and Rehabilitation, and the American Board of Psychiatry and Neurology each provide certification for a subspecialty in pain management following fellowship training which is recognized by the American Board of Medical Specialties (ABMS) or the American Osteopathic Association Bureau of Osteopathic Specialists (AOABOS). As the field of pain medicine has grown rapidly, many practitioners have entered the field, some non-ACGME board-certified.

Medical cannabis research

From Wikipedia, the free encyclopedia

Medical cannabis research includes any medical research on using cannabis as a treatment for any medical condition. For reasons including increased popular support of cannabis use, a trend of cannabis legalization, and the perception of medical usefulness, more scientists are doing medical cannabis research. Medical cannabis is unusually broad as a treatment for many conditions, each of which has its own state of research. Similarly, various countries conduct and respond to medical cannabis research in different ways.

Ethics

Cannabis use as a medical treatment has risen globally since 2008 for a variety of reasons including increasing popular support for cannabis legalization and increased incidence of chronic pain among patients. While medical cannabis use is increasing, there are major social and legal barriers which lead to cannabis research proceeding more slowly and differently from standard medical research. Reasons why cannabis is unusual as a treatment include that it is not a patented drug owned by the pharmaceutical industry, and that its legal status as a medical treatment is ambiguous even where it is legal to use, and that cannabis use carries outside the norm of a typical medical treatment. The ethics around cannabis research is in a state of rapid change.

Research by region

United States

Research on the medical benefits of cannabis has been hindered by various federal regulations, including its Schedule I classification. To conduct research on cannabis, approval must be obtained from the Food and Drug Administration, and a license must be obtained from the Drug Enforcement Administration specific to Schedule I drugs. The FDA has 30 days to respond to proposals, while the DEA licensing can take over a year to complete. Prior to June 2015, cannabis research also required approval from the US Public Health Service. The PHS review was not performed for any other Schedule I drugs, and had no deadline imposed.

In addition to the FDA and DEA (and former PHS) requirements, the National Institute on Drug Abuse must review and approve all cannabis research. The NIDA is the only source licensed by the federal government for the cultivation and provision of cannabis, and the NIDA will not provide cannabis without first approving the research. This monopoly maintained by the DEA does not exist for other Schedule I drugs, and there is no deadline established for the NIDA review either. The quality and potency of cannabis supplied by NIDA has also been called into question by some researchers.

As a result of these requirements that have been imposed in the US, studies involving cannabis have been delayed for years in some cases, and a number of medical organizations have called for federal policy to be reformed.

A 2016 review assess the current status and prospects for development of CBD and CBD-dominant preparations for medical use in the United States, examining its neuroprotective, antiepileptic, anxiolytic, antipsychotic, and antiinflammatory properties.

In April 2018, after 5 years of research, Sanjay Gupta backed medical marijuana for conditions such as epilepsy and multiple sclerosis. He believes that medical marijuana is safer than opioid for pain management.

Research by medical condition

Cancer

Cannabinoids have been shown to exhibit some anti-cancer effects in laboratory experiments, although there has been little research into their use as a cancer treatment in people. Laboratory experiments have suggested that cannabis and cannabinoids have anticarcinogenic and antitumor effects, including a potential effect on breast- and lung-cancer cells. The National Cancer Institute reports that as of November 2013 there have been no clinical trials on the use of cannabis to treat cancer in people, and only one small study using delta-9-THC that reported potential antitumoral activity. While cannabis may have potential for refractory cancer pain, use as an antiemetic, and as an antitumor agent, much of the evidence comes from outdated or small studies, or animal experiments.

Although there is ongoing research, claims that cannabis has been proved to cure cancer are, according to Cancer Research UK, both prevalent on the internet and "highly misleading".

There is no good evidence that cannabis use helps reduce the risk of getting cancer. Whether smoking cannabis increases cancer risk in general is difficult to establish since it is often smoked mixed with tobacco – a known carcinogen – and this complicates research. Cannabis use is linked to an increased risk of a type of testicular cancer.

The association of cannabis use with head and neck carcinoma may differ by tumor site, with both possible pro- and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, confounds and misclassification of cannabis exposure.

Dementia

Cannabinoids have been proposed to have the potential for lessening the effects of Alzheimer's disease. A 2012 review of the effect of cannabinoids on brain ageing found that "clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing". A 2009 Cochrane review said that the "one small randomized controlled trial [that] assessed the efficacy of cannabinoids in the treatment of dementia ... [had] ... poorly presented results and did not provide sufficient data to draw any useful conclusions".

Diabetes

There is emerging evidence that cannabidiol may help slow cell damage in diabetes mellitus type 1. There is a lack of meaningful evidence of the effects of medical cannabis use on people with diabetes; a 2010 review concluded that "the potential risks and benefits for diabetic patients remain unquantified at the present time".

Epilepsy

A 2016 review in the New England Journal of Medicine said that although there was a lot of hype and anecdotes surrounding medical cannabis and epilepsy, "current data from studies in humans are extremely limited, and no conclusions can be drawn". The mechanisms by which cannabis may be effective in the treatment of epilepsy remain unclear.

Some reasons for the lack of clinical research have been the introduction of new synthetic and more stable pharmaceutical anticonvulsants, the recognition of important adverse side effects, and legal restrictions to the use of cannabis-derived medicines – although in December 2015, the DEA (United States Drug Enforcement Administration) has eased some of the regulatory requirements for conducting FDA-approved clinical trials on cannabidiol (CBD).

Epidiolex, a cannabis-based product developed by GW Pharmaceuticals for experimental treatment of epilepsy, underwent stage-two trials in the US in 2014.

A 2017 study found that cannabidiol decreased the rate of seizures in those with Dravet syndrome but increased the rate of sleepiness and trouble with the liver.

Glaucoma

In 2009, the American Glaucoma Society noted that while cannabis can help lower intraocular pressure, it recommended against its use because of "its side effects and short duration of action, coupled with a lack of evidence that its use alters the course of glaucoma". As of 2008 relatively little research had been done concerning therapeutic effects of cannabinoids on the eyes.

Tourette syndrome

A 2007 review of the history of medical cannabis said cannabinoids showed potential therapeutic value in treating Tourette syndrome (TS). A 2005 review said that controlled research on treating TS with dronabinol showed the patients taking the pill had a beneficial response without serious adverse effects; a 2000 review said other studies had shown that cannabis "has no effects on tics and increases the individuals inner tension".

A 2009 Cochrane review examined the two controlled trials to date using cannabinoids of any preparation type for the treatment of tics or TS (Muller-Vahl 2002, and Muller-Vahl 2003). Both trials compared delta-9-THC; 28 patients were included in the two studies (8 individuals participated in both studies). Both studies reported a positive effect on tics, but "the improvements in tic frequency and severity were small and were only detected by some of the outcome measures". The sample size was small and a high number of individuals either dropped out of the study or were excluded. The original Muller-Vahl studies reported individuals who remained in the study; patients may drop out when adverse effects are too high or efficacy is not evident. The authors of the original studies acknowledged few significant results after Bonferroni correction.

Cannabinoid medication might be useful in the treatment of the symptoms in patients with TS, but the 2009 review found that the two relevant studies of cannibinoids in treating tics had attrition bias, and that there was "not enough evidence to support the use of cannabinoids in treating tics and obsessive compulsive behaviour in people with Tourette's syndrome".

Other conditions

Anecdotal evidence and pre-clinical research has suggested that cannabis or cannabinoids may be beneficial for treating Huntington's disease or Parkinson's disease, but follow-up studies of people with these conditions have not produced good evidence of therapeutic potential. A 2001 paper argued that cannabis had properties that made it potentially applicable to the treatment of amyotrophic lateral sclerosis, and on that basis research on this topic should be permitted, despite the legal difficulties of the time.

A 2005 review and meta-analysis said that bipolar disorder was not well-controlled by existing medications and that there were "good pharmacological reasons" for thinking cannabis had therapeutic potential, making it a good candidate for further study.

Cannabinoids have been proposed for the treatment of primary anorexia nervosa, but have no measurable beneficial effect. The authors of a 2003 paper argued that cannabinoids might have useful future clinical applications in treating digestive diseases. Laboratory experiments have shown that cannabinoids found in marijuana may have analgesic and anti-inflammatory effects.

In 2014, the American Academy of Neurology reviewed all available findings levering the use of marijuana to treat brain diseases. The result was that the scientific evidence is weak that cannabis in any form serves as medicinal for curing or alleviating neurological disorders. To ease multiple sclerosis patients' stiffness, which may be accomplished by their taking cannabis extract by mouth or as a spray, there is support. The academy has published new guidelines on the use of marijuana pills and sprays in the treatment of MS.

Cannabis is being investigated for its possible use in inflammatory bowel disease but as of 2014 there is only weak evidence for its benefits as a treatment.

A 2007 review said cannabidiol had shown potential to relieve convulsion, inflammation, cough, congestion and nausea, and to inhibit cancer cell growth. Preliminary studies have also shown potential over psychiatric conditions such as anxiety, depression, and psychosis. Because cannabidiol relieves the aforementioned symptoms, cannabis strains with a high amount of CBD may benefit people with multiple sclerosis or frequent anxiety attacks.

Bjørn Lomborg: No, renewables are not taking over the world.

By Anthony Watts

Original link:  https://wattsupwiththat.com/2019/03/30/bjorn-lomborg-no-renewables-are-not-taking-over-the-world/?fbclid=IwAR0fy6E5JtTaVvFO5GJk6FiWyeJ-X74T5qbAJRvvCpBul2FvU6YrjFzqM5s March 30, 2019

Bjørn Lomborg writes on his Facebook page:

We’re constantly being told how renewables are close to taking over the world.

We’re told they are so cheap they’ll undercut fossil fuels and reign supreme pretty soon.

That would be nice. If they were cheaper, they could cut our soaring electricity bills. With cheap and abundant power, they would push development for the world’s poorest. And it would, of course, fix climate change.

Unfortunately, it is also mostly an illusion. This short video shows you why renewables are not likely to take over the world anytime soon.

It is also crucial for us to know. The misapprehension that renewables are just about to take over makes many believe that we have all the technologies needed to go to zero CO₂. That we just need more political will. Yet, nothing could be further from the truth.

Jim Hansen, Al Gore’s climate advisor and the scientist who literally started the global warming worry in 1988 puts it clearly: “Suggesting that renewables will let us phase rapidly off fossil fuels in the United States, China, India, or the world as a whole is almost the equivalent of believing in the Easter Bunny and Tooth Fairy.”

To fix climate change, we need to stop believing in the Easter Bunny and start realizing that without much better, cheaper, green technology, we won’t transition away from fossil fuels. That’s why we need to invest a lot more into green energy R&D. If we can help innovate green energy to become cheaper and better than fossil fuels, *everyone* will switch. Not just rich, well-meaning first-worlders, but also China, India and Africa.

The video shows how we’ve spent the last two centuries getting *off* renewable energy. In 1800, most energy came from our own back-breaking work, along with wood (for fire) and draught animals. Wind and water contributed in most places a tiny fraction. The 6% fossil fuel was almost entirely England starting up the industrial revolution with coal.

What made us rich over the next two centuries, was cheap and plentiful energy, almost exclusively from fossil fuels. It made it possible for us to have machines do much more of the hard work. By the end of the nineteenth century human labor made up 94 percent of all industrial work in the US. Today, it constitutes just 8 percent.

For the past half century, renewable energy has hovered around 13-14%, most of it wood burning in the world’s poorest regions (leading to the world’s leading environmental killer, indoor air pollution).

The International Energy Agency estimates that if *everyone* live up to their Paris promises (and other promises), we’ll get to 20% in 2040. Since almost no-one is actually performing on their Paris promises, the business-as-usual scenario of 16.5% is more likely.

The UN’s Climate Panel has devised 5 main scenarios (the SSPs), showcasing development over the rest of the century. Even the greenest scenario, the SSP1, will by the end of the century just get 45% of its energy from renewables.

The UN scenarios are without explicit climate policies, but the stories of SSP1 is centered around environmental focus: “The world shifts gradually, but pervasively, toward a more sustainable path, emphasizing more inclusive development that respects perceived environmental boundaries. Management of the global commons slowly improves, educational and health investments accelerate the demographic transition, and the emphasis on economic growth shifts toward a broader emphasis on human well-being. Driven by an increasing commitment to achieving development goals, inequality is reduced both across and within countries. Consumption is oriented toward low material growth and lower resource and energy intensity.”

To give you a sense of this: the SSP1 expects that by 2100, the average rich person in the world will have to get by on *half* the energy we have today (and this is final energy, not TPES). The average person in the developing world, while getting more energy than today will have to live with never getting to half on what the average rich person gets today. This is a scenario with little development, populated by very modest people and overall a very unrealistic world.

Sources:

Hansen equivalent to Tooth Fairy, https://dotearth.blogs.nytimes.com/…/jim-hansen-presses-t…/…

Data is in TPES or TPED (but not dramatically different for final energy, with SSP1 in 2100 getting 39% of final energy from fossil fuels and 9% from wood.

“A brief history of energy” Roger Fouquet, International Handbook of the Economics of Energy, 2009 and International Energy Agency, data from 1971-2017 projections to 2040 from IEA latest World Energy Outlook 2018 (November 2018) and all five UN SSP scenarios, which are accessible here:https://tntcat.iiasa.ac.at/SspDb, and discussed here:www.sciencedirect.com/science/article/pii/S0959378016300681

Effects of cannabis

From Wikipedia, the free encyclopedia

Cannabis

 

Chemical compounds in the Cannabis plant, including 400 different cannabinoids such as tetrahydrocannabinol (THC), allow its drug to have various psychological and physiological effects on the human body. Different plants of the genus Cannabis contain different and often unpredictable concentrations of THC and other cannabinoids and hundreds of other molecules that have a pharmacological effect, so that the final net effect cannot reliably be foreseen. 

Acute effects while under the influence can include euphoria and anxiety. Cannabidiol (CBD), another cannabinoid found in cannabis in varying amounts, has been shown to alleviate the adverse effects of THC that some consumers experience. When ingested orally, THC can produce stronger psychotropic effects than when inhaled. At doses exceeding the psychotropic threshold, users may experience adverse side effects such as anxiety and panic attacks that can result in increased heart rate and changes in blood pressure. 

In the United States research about medical cannabis has been hindered by federal law. Smoking any substance could possibly carry similar risks as smoking tobacco due to carcinogens in all smoke, and the ultimate conclusions on these factors are disputed.

Cannabis use disorder is defined as a medical diagnosis in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Effects

The structural formula of tetrahydrocannabinol

 

Tetrahydrocannabivarin

 

Cannabidiol

 

Cannabinol

 

Cannabivarin

 

Cannabidivarin

Cannabinoids and cannabinoid receptors

The most prevalent psychoactive substances in cannabis are cannabinoids, particularly THC. Some varieties, having undergone careful selection and growing techniques, can yield as much as 34% THC. Another psychoactive cannabinoid present in Cannabis sativa is tetrahydrocannabivarin (THCV), but it is only found in small amounts and is a cannabinoid antagonist.

There are similar compounds in cannabis that do not exhibit psychoactive response but are obligatory for functionality: cannabidiol (CBD), an isomer of THC; cannabivarin (CBV), an analog of cannabinol (CBN) with a different side chain, cannabidivarin (CBDV), an analog of CBD with a different side chain, and cannabinolic acid. How these other compounds interact with THC is not fully understood. Some clinical studies have proposed that CBD acts as a balancing agent to regulate the strength of the psychoactive agent THC. CBD is believed to regulate the metabolism of THC by inactivating cytochrome P450, an important class of enzymes that metabolize drugs. Experiments in which babies were treated with CBD followed by THC showed that CBD was associated with a substantial increase in brain concentrations of THC and its major metabolites, most likely because it decreased the rate of clearance of THC from the body. Cannabis cofactors have also been linked to lowering body temperature, modulating immune function, and cell protection. The essential oil of cannabis contains many fragrant terpenoids which may synergize with the cannabinoids to produce their unique effects. THC is converted rapidly to 11-hydroxy-THC, which is also pharmacologically active, so the euphoria outlasts measurable THC levels in blood.

THC and cannabidiol are neuroprotective antioxidants. Research on rats has demonstrated that THC prevents hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was significantly more protective than either vitamin E or vitamin C.

The cannabinoid receptor is a typical G protein-coupled receptor. A characteristic of this type of receptor is the distinct pattern of how the molecule spans the cell membrane seven times. Cannabinoid receptors are located on the cell membrane, and both outside (extracellularly) and inside (intracellularly) the cell membrane. CB1 receptors, the bigger of the two, are extraordinarily abundant in the brain: 10 times more plentiful than the μ-opioid receptors responsible for the effects of morphine. CB2 receptors are structurally different (the sequence similarity between the two subtypes of receptors is 44%), found only on cells of the immune system, and seems to function similarly to its CB1 counterpart. CB2 receptors are most prevalent on B-cells, natural killer cells, and monocytes, but can also be found on polymorphonuclear neutrophil cells, T8 cells, and T4 cells. In the tonsils the CB2 receptors appear to be restricted to B-lymphocyte-enriched areas. 

THC and its endogenous equivalent anandamide additionally interact with glycine receptors.

Biochemical mechanisms in the brain

Cannabinoids usually contain a 1,1'-di-methyl-pyran ring, a variedly derivatized aromatic ring and a variedly unsaturated cyclohexyl ring and their immediate chemical precursors, constituting a family of about 60 bi-cyclic and tri-cyclic compounds. Like most other neurological processes, the effects of cannabis on the brain follow the standard protocol of signal transduction, the electrochemical system of sending signals through neurons for a biological response. It is now understood that cannabinoid receptors appear in similar forms in most vertebrates and invertebrates and have a long evolutionary history of 500 million years. The binding of cannabinoids to cannabinoid receptors decrease adenylyl cyclase activity, inhibit calcium N channels, and disinhibit K⁺_A channels. There are at least two types of cannabinoid receptors (CB1 and CB2).

The CB1 receptor is found primarily in the brain and mediates the psychological effects of THC. The CB2 receptor is most abundantly found on cells of the immune system. Cannabinoids act as immunomodulators at CB2 receptors, meaning they increase some immune responses and decrease others. For example, nonpsychotropic cannabinoids can be used as a very effective anti-inflammatory. The affinity of cannabinoids to bind to either receptor is about the same, with only a slight increase observed with the plant-derived compound CBD binding to CB2 receptors more frequently. Cannabinoids likely have a role in the brain’s control of movement and memory, as well as natural pain modulation. It is clear that cannabinoids can affect pain transmission and, specifically, that cannabinoids interact with the brain's endogenous opioid system and may affect dopamine transmission.

Sustainability in the body

Most cannabinoids are lipophilic (fat soluble) compounds that are easily stored in fat, thus yielding a long elimination half-life relative to other recreational drugs. The THC molecule, and related compounds, are usually detectable in drug tests from 3 days up to 10 days according to Redwood Laboratories; long-term users can produce positive tests for two to three months after ceasing cannabis use.

Toxicities

Related to cannabinoids

No fatal overdoses with cannabis use have been reported. A review published in the British Journal of Psychiatry in February 2008 said that "no deaths directly due to acute cannabis use have ever been reported".

THC, the principal psychoactive constituent of the cannabis plant, has an extremely low toxicity and the amount that can enter the body through the consumption of cannabis plants poses no threat of death. In dogs, the minimum lethal dose of THC is over 3 g/kg.

According to the Merck Index, the LD₅₀ of THC (the dose which causes the death of 50% of individuals) is 1270 mg/kg for male rats and 730 mg/kg for female rats from oral consumption in sesame oil, and 42 mg/kg for rats from inhalation.

It is important though to note that cannabinoids and other molecules present in cannabis can alter the metabolism of other drugs, especially due to competition for clearing metabolic pathways such as cytochromes CYP450, thus leading to drug toxicities by medications that the person consuming cannabis may be taking.

Related to smoking

A 2007 study found that while tobacco and cannabis smoke are quite similar, cannabis smoke contained higher amounts of ammonia, hydrogen cyanide, and nitrogen oxides, but lower levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs). This study found that directly inhaled cannabis smoke contained as much as 20 times as much ammonia and 5 times as much hydrogen cyanide as tobacco smoke and compared the properties of both mainstream and sidestream (smoke emitted from a smouldering 'joint' or 'cone') smoke. Mainstream cannabis smoke was found to contain higher concentrations of selected polycyclic aromatic hydrocarbons (PAHs) than sidestream tobacco smoke. However, other studies have found much lower disparities in ammonia and hydrogen cyanide between cannabis and tobacco, and that some other constituents (such as polonium-210, lead, arsenic, nicotine, and tobacco-specific nitrosamines) are either lower or non-existent in cannabis smoke.

Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in tobacco smoke or cigars. Over fifty known carcinogens have been identified in cannabis smoke. These include nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene. Marijuana smoke was listed as a cancer agent in California in 2009. A study by the British Lung Foundation published in 2012 identifies cannabis smoke as a carcinogen and also finds awareness of the danger is low compared with the high awareness of the dangers of smoking tobacco particularly among younger users. Other observations include possible increased risk from each cigarette; lack of research on the effect of cannabis smoke alone; low rate of addiction compared to tobacco; and episodic nature of cannabis use compared to steady frequent smoking of tobacco. Professor David Nutt, a UK drug expert, points out that the study cited by the British Lung Foundation has been accused of both "false reasoning" and "incorrect methodology". Further, he notes that other studies have failed to connect cannabis with lung cancer, and accuses the BLF of "scaremongering over cannabis".

Short-term effects

When smoked, the short-term effects of cannabis manifest within seconds and are fully apparent within a few minutes, typically lasting for 1–3 hours, varying by the person and the strain of cannabis. After oral ingestion of cannabis, the onset of effect is delayed relative to smoking, taking 30 minutes to 2 hours, but the duration is prolonged due to continued slow absorption. The duration of noticeable effects has been observed to diminish after prolonged, repeated use and the development of increased tolerance to cannabinoids.

Psychological effects

A Hindu man smoking cannabis in Kolkata, India.

 

The psychoactive effects of cannabis, known as a "high", are subjective and vary among persons and the method of use. 

When THC enters the blood stream and reaches the brain, it binds to cannabinoid receptors. The endogenous ligand of these receptors is anandamide, the effects of which THC emulates. This agonism of the cannabinoid receptors results in changes in the levels of various neurotransmitters, especially dopamine and norepinephrine; neurotransmitters which are closely associated with the acute effects of cannabis ingestion, such as euphoria and anxiety. Some effects may include a general alteration of conscious perception, euphoria, feelings of well-being, relaxation or stress reduction, increased appreciation of the arts, including humor and music (especially discerning its various components/instruments), joviality, metacognition and introspection, enhanced recollection (episodic memory), increased sensuality, increased awareness of sensation, increased libido, and creativity. Abstract or philosophical thinking, disruption of linear memory and paranoia or anxiety are also typical. Anxiety is the most commonly reported side effect of smoking marijuana. Between 20 and 30 percent of recreational users experience intense anxiety and/or panic attacks after smoking cannabis, however, some report anxiety only after not smoking cannabis for a prolonged period of time. Inexperience and use in an unfamiliar environment are major contributing factors to this anxiety. Cannabidiol (CBD), another cannabinoid found in cannabis in varying amounts, has been shown to ameliorate the adverse effects of THC, including anxiety, that some consumers experience.

Cannabis produces many other subjective effects, including an increased enjoyment of food taste and aroma, and marked distortions in the perception of time (where experiencing a "rush" of ideas can create the subjective impression of much time passing). At higher doses, effects can include altered body image, auditory and/or visual illusions, pseudohallucinations, and ataxia from selective impairment of polysynaptic reflexes. In some cases, cannabis can lead to acute psychosis and dissociative states such as depersonalization and derealization.

Any episode of acute psychosis that accompanies cannabis use usually abates after 6 hours, but in rare instances, heavy users may find the symptoms continuing for many days. If the episode is accompanied by aggression or sedation, physical restraint may be necessary.

While psychoactive drugs are typically categorized as stimulant, depressant, or hallucinogen, cannabis exhibits a mix of all of them, perhaps leaning more towards hallucinogenic or psychedelic properties, though with other effects quite pronounced. THC is considered the primary active component of the cannabis plant. Scientific studies have suggested that other cannabinoids like CBD may also play a significant role in its psychoactive effects.

Somatic effects

Bloodshot eye

 

Some of the short-term physical effects of cannabis use include increased heart rate, dry mouth, reddening of the eyes (congestion of the conjunctival blood vessels), a reduction in intra-ocular pressure, muscle relaxation and a sensation of cold or hot hands and feet and / or flushed face.

Electroencephalography or EEG shows somewhat more persistent alpha waves of slightly lower frequency than usual. Cannabinoids produce a "marked depression of motor activity" via activation of neuronal cannabinoid receptors belonging to the CB1 subtype.

Duration

Peak levels of cannabis-associated intoxication occur approximately 30 minutes after smoking it and last for several hours.

Smoked

The total short-term duration of cannabis use when smoked depends on the potency, method of smoking – e.g. whether pure or in conjunction with tobacco – and how much is smoked. Peak levels of intoxication typically last an average of three to four hours.

Oral

When taken orally (in the form of capsules, food or drink), the psychoactive effects take longer to manifest and generally last longer, typically lasting for an average of four to ten hours after consumption. Very high doses may last even longer. Also, oral ingestion use eliminates the need to inhale toxic combustion products created by smoking and therefore negates the risk of respiratory harm associated with cannabis smoking.

Neurological effects

The areas of the brain where cannabinoid receptors are most prevalent are consistent with the behavioral effects produced by cannabinoids. Brain regions in which cannabinoid receptors are very abundant are the basal ganglia, associated with movement control; the cerebellum, associated with body movement coordination; the hippocampus, associated with learning, memory, and stress control; the cerebral cortex, associated with higher cognitive functions; and the nucleus accumbens, regarded as the reward center of the brain. Other regions where cannabinoid receptors are moderately concentrated are the hypothalamus, which regulates homeostatic functions; the amygdala, associated with emotional responses and fears; the spinal cord, associated with peripheral sensations like pain; the brain stem, associated with sleep, arousal, and motor control; and the nucleus of the solitary tract, associated with visceral sensations like nausea and vomiting.

Experiments on animal and human tissue have demonstrated a disruption of short-term memory formation, which is consistent with the abundance of C receptors on the hippocampus, the region of the brain most closely associated with memory. Cannabinoids inhibit the release of several neurotransmitters in the hippocampus such as acetylcholine, norepinephrine, and glutamate, resulting in a decrease in neuronal activity in that area. 

In in-vitro experiments THC at extremely high concentrations, which could not be reached with commonly consumed doses, caused competitive inhibition of the AChE enzyme and inhibition of β-amyloid peptide aggregation, implicated in the development of Alzheimer's disease. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of A aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may impact the progression of this debilitating disease.

Effects on driving

While several studies have shown increased risk associated with cannabis use by drivers, other studies have not found increased risk. Cannabis usage has been shown in some studies to have a negative effect on driving ability. The British Medical Journal indicated that "drivers who consume cannabis within three hours of driving are nearly twice as likely to cause a vehicle collision as those who are not under the influence of drugs or alcohol".

In Cannabis and driving: a review of the literature and commentary, the United Kingdom's Department for Transport reviewed data on cannabis and driving, finding although impaired, "subjects under cannabis treatment appear to perceive that they are indeed impaired. Where they can compensate, they do...". In a review of driving simulator studies, researchers note that "even in those who learn to compensate for a drug's impairing effects, substantial impairment in performance can still be observed under conditions of general task performance (i.e. when no contingencies are present to maintain compensated performance)."

A 2012 meta-analysis found that acute cannabis use increased the risk of an automobile crash. An extensive 2013 review of 66 studies regarding crash risk and drug use found that cannabis was associated with minor, but not statistically significant increased odds of injury or fatal accident.

In the largest and most precisely controlled study of its kind carried out by the U.S. Department of Transportation’s National Highway Traffic Safety Administration, it was found that other "studies that measure the presence of THC in the drivers' blood or oral fluid, rather than relying on self-report tend to have much lower (or no) elevated crash risk estimates. Likewise better controlled studies have found lower (or no) elevated crash risk estimates". The study found that "after adjusting for age, gender, race and alcohol use, drivers who tested positive for marijuana were no more likely to crash than those who had not used any drugs or alcohol prior to driving".

On the other hand, a recent study of Journal of Transport & Health indicated that the numbers of fatal crashes involving marijuana after the recreational marijuana legalization or decriminalization have significantly increased in Colorado, Washington, and Massachusetts.

Cardiovascular effects

Short-term (one to two hours) effects on the cardiovascular system can include increased heart rate, dilation of blood vessels, and fluctuations in blood pressure. There are medical reports of occasional heart attacks or myocardial infarction, stroke and other cardiovascular side effects. Marijuana's cardiovascular effects are not associated with serious health problems for most young, healthy users. Researchers reported in the International Journal of Cardiology, "Marijuana use by older people, particularly those with some degree of coronary artery or cerebrovascular disease, poses greater risks due to the resulting increase in catecholamines, cardiac workload, and carboxyhemoglobin levels, and concurrent episodes of profound postural hypotension. Indeed, marijuana may be a much more common cause of myocardial infarction than is generally recognized. In day-to-day practice, a history of marijuana use is often not sought by many practitioners, and even when sought, the patient's response is not always truthful".

A 2013 analysis of 3,886 myocardial infarction survivors over an 18-year period showed "no statistically significant association between marijuana use and mortality".

A 2008 study by the National Institutes of Health Biomedical Research Centre in Baltimore found that heavy, chronic smoking of marijuana (138 joints per week) changed blood proteins associated with heart disease and stroke.

A 2000 study by researchers at Boston's Beth Israel Deaconess Medical Center, Massachusetts General Hospital and Harvard School of Public Health found that a middle-age person's risk of heart attack rises nearly fivefold in the first hour after smoking marijuana, "roughly the same risk seen within an hour of sexual activity".

Cannabis arteritis is a very rare peripheral vascular disease similar to Buerger's disease. There were about 50 confirmed cases from 1960 to 2008, all of which occurred in Europe.

Combination with other drugs

A confounding factor in cannabis research is the prevalent usage of other recreational drugs, especially alcohol and nicotine. Such complications demonstrate the need for studies on cannabis that have stronger controls, and investigations into alleged symptoms of cannabis use that may also be caused by tobacco. Some critics question whether agencies doing the research make an honest effort to present an accurate, unbiased summary of the evidence, or whether they "cherry-pick" their data to please funding sources which may include the tobacco industry or governments dependent on cigarette tax revenue; others caution that the raw data, and not the final conclusions, are what should be examined.

The Australian National Household Survey of 2001 showed that cannabis in Australia is rarely used without other drugs. 95% of cannabis users also drank alcohol; 26% took amphetamines; 19% took ecstasy and only 2.7% reported not having used any other drug with cannabis. While research has been undertaken on the combined effects of alcohol and cannabis on performing certain tasks, little research has been conducted on the reasons why this combination is so popular. Evidence from a controlled experimental study undertaken by Lukas and Orozco suggests that alcohol causes THC to be absorbed more rapidly into the blood plasma of the user. Data from the Australian National Survey of Mental Health and Wellbeing found that three-quarters of recent cannabis users reported using alcohol when cannabis was not available, this suggests that the two are substitutes.

Memory and learning

Studies on cannabis and memory are hindered by small sample sizes, confounding drug use, and other factors. The strongest evidence regarding cannabis and memory focuses on its temporary negative effects on short-term and working memory.

In a 2001 study looking at neuropsychological performance in long-term cannabis users, researchers found "some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use". On his studies regarding cannabis use, lead researcher and Harvard professor Harrison Pope said he found marijuana is not dangerous over the long term, but there are short-term effects. From neuropsychological tests, Pope found that chronic cannabis users showed difficulties, with verbal memory in particular, for "at least a week or two" after they stopped smoking. Within 28 days, memory problems vanished and the subjects "were no longer distinguishable from the comparison group". Researchers from the University of California, San Diego School of Medicine failed to show substantial, systemic neurological effects from long-term recreational use of cannabis. Their findings were published in the July 2003 issue of the Journal of the International Neuropsychological Society. The research team, headed by Dr Igor Grant, found that cannabis use did affect perception, but did not cause permanent brain damage. Researchers looked at data from 15 previously published controlled studies involving 704 long-term cannabis users and 484 nonusers. The results showed long-term cannabis use was only marginally harmful on the memory and learning. Other functions such as reaction time, attention, language, reasoning ability, perceptual and motor skills were unaffected. The observed effects on memory and learning, they said, showed long-term cannabis use caused "selective memory defects", but that the impact was "of a very small magnitude". A study at Johns Hopkins University School of Medicine showed that very heavy use of marijuana is associated with decrements in neurocognitive performance even after 28 days of abstinence.

Appetite

The feeling of increased appetite following the use of cannabis has been documented for hundreds of years, and is known colloquially as "the munchies" in the English-speaking world. Clinical studies and survey data have found that cannabis increases food enjoyment and interest in food. A 2015 study suggests that cannabis triggers uncharacteristic behaviour in POMC neurons, which are usually associated with decreasing hunger. Rarely, chronic users experience a severe vomiting disorder, cannabinoid hyperemesis syndrome, after smoking and find relief by taking hot baths.

Endogenous cannabinoids ("endocannabinoids") were discovered in cow's milk and soft cheeses. Endocannabinoids are also found in human breast milk. It is widely accepted that the neonatal survival of many species "is largely dependent upon their suckling behavior, or appetite for breast milk" and recent research has identified the endogenous cannabinoid system to be the first neural system to display complete control over milk ingestion and neonatal survival. It is possible that "cannabinoid receptors in our body interact with the cannabinoids in milk to stimulate a suckling response in newborns so as to prevent growth failure".

Pathogens and microtoxins

Most microorganisms found in cannabis only affect plants and not humans, but some microorganisms, especially those that proliferate when the herb is not correctly dried and stored, can be harmful to humans. Some users may store marijuana in an airtight bag or jar in a refrigerator to prevent fungal and bacterial growth.

Fungi

Aspergillus fumigatus

 

The fungi Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus parasiticus, Aspergillus tamarii, Aspergillus sulphureus, Aspergillus repens, Mucor hiemalis (not a human pathogen), Penicillium chrysogenum, Penicillium italicum and Rhizopus nigrans have been found in moldy cannabis. Aspergillus mold species can infect the lungs via smoking or handling of infected cannabis and cause opportunistic and sometimes deadly aspergillosis. Some of the microorganisms found create aflatoxins, which are toxic and carcinogenic. Researchers suggest that moldy cannabis should thus be discarded to avoid these serious risks.

Mold is also found in smoke from mold-infected cannabis, and the lungs and nasal passages are a major means of contracting fungal infections. Levitz and Diamond (1991) suggested baking marijuana in home ovens at 150 °C [302 °F], for five minutes before smoking. Oven treatment killed conidia of A. fumigatus, A. flavus and A. niger, and did not degrade the active component of marijuana, tetrahydrocannabinol (THC)."

Bacteria

Cannabis contaminated with Salmonella muenchen was positively correlated with dozens of cases of salmonellosis in 1981. "Thermophilic actinomycetes" were also found in cannabis.

Long-term effects

Exposure to marijuana may have biologically-based physical, mental, behavioral and social health consequences and is "associated with diseases of the liver (particularly with co-existing hepatitis C), lungs, heart, eyesight and vasculature" according to a 2013 literature review by Gordon and colleagues. The association with these diseases has only been reported in cases where people have smoked cannabis. The authors cautioned that "evidence is needed, and further research should be considered, to prove causal associations of marijuana with many physical health conditions".

Cannabis use disorder is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a condition requiring treatment. Several drugs have been investigated in an attempt to ameliorate the symptoms of stopping cannabis use. Such drugs include bupropion, divalproex, nefazodone, lofexidine, and dronabinol. Of these, dronabinol has proven the most effective.

Effects in pregnancy

Cannabis consumption in pregnancy might be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits in offspring based on animal studies, although there is limited evidence for this in humans at this time. A 2012 systematic review found although it was difficult to draw firm conclusions, there was some evidence that prenatal exposure to cannabis was associated with "deficits in language, attention, areas of cognitive performance, and delinquent behavior in adolescence". A report prepared for the Australian National Council on Drugs concluded cannabis and other cannabinoids are contraindicated in pregnancy as it may interact with the endocannabinoid system.