Difference between revisions of "Effects of cannabis"

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The primary effects of cannabis are caused by the chemical compounds in the plant, including cannabinoids such as tetrahydrocannabinol (THC), which is only one of about 400 different cannabinoids. Cannabis has psychological and physiological effects on the human body.

In large enough doses, THC can induce auditory and visual hallucinations. Acute effects while under the influence can include both euphoria and anxiety. Concerns have been raised about the potential for long-term cannabis consumption to increase risk for schizophrenia, depersonalization disorder, bipolar disorders, and major depression,however studies are inconclusive, and research about medical benefits of cannabis has been hindered by federal law. Permits tend only to extend in funding research seeking to prove claims of harmful effects in the use of marijuana. So far, no long term effects are linked to the chemicals in cannabis itself but rather to smoking it. Smoking any substance will carry the same risk as smoking marijuana due to carcinogens in all smoke. and the ultimate conclusions on these factors are disputed.[10] The evidence of long-term effects on memory is preliminary and hindered by confounding factors.

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

Contents

   1 Biochemical effects
       1.1 Cannabinoids and cannabinoid receptors
       1.2 Biochemical mechanisms in the brain
       1.3 Sustainability in the body
       1.4 Toxicity
   2 Short-term effects
       2.1 Psychoactive effects
       2.2 Somatic effects
       2.3 Duration
           2.3.1 Smoked
           2.3.2 Oral
       2.4 Neurological effects
       2.5 Effects on driving
       2.6 Cardiovascular effects
       2.7 Combination with other drugs
       2.8 Memory and learning
       2.9 Appetite
       2.10 Pathogens and microtoxins
           2.10.1 Fungi
           2.10.2 Bacteria
   3 Long-term effects
   4 Effects in pregnancy
   5 See also
   6 References
   7 External links

Biochemical effects Cannabinoids and cannabinoid receptors

The most prevalent psychoactive substances in cannabis are cannabinoids, most notably THC. Some varieties, having undergone careful selection and growing techniques, can yield as much as 29% THC. Another psychoactive cannabinoid present in Cannabis sativa is tetrahydrocannabivarin (THCV), but it is only found in small amounts and is a cannabinoid antagonist.

In addition, there are also similar compounds contained in cannabis that do not exhibit any psychoactive response but are obligatory for functionality: cannabidiol (CBD), an isomer of THC; cannabinol (CBN), an oxidation product of THC; cannabivarin (CBV), an analog of 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 force to regulate the strength of the psychoactive agent THC. CBD is also believed to regulate the body’s metabolism of THC by inactivating cytochrome P450, an important class of enzymes that metabolize drugs. Experiments in which mice were treated with CBD followed by THC showed that CBD treatment 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 cofactor compounds have also been linked to lowering body temperature, modulating immune functioning, 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 drug effect outlasts measurable THC levels in blood.

THC and cannabidiol are also neuroprotective antioxidants. Research in rats has indicated that THC prevented 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 member of the largest known family of receptors called a G protein-coupled receptor. A signature of this type of receptor is the distinct pattern of how the receptor molecule spans the cell membrane seven times. The location of cannabinoid receptors exists 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 μ-opioid receptors, the 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 commonly 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 endogenous anandamide additionally interact with glycine receptors.

Biochemical mechanisms in the brain See also: Cannabis (drug) § Mechanism of action

In 1990 the discovery of cannabinoid receptors located throughout the brain and body, along with endogenous cannabinoid neurotransmitters like anandamide (a lipid material derived ligand from arachidonic acid), suggested that the use of cannabis affects the brain in the same manner as a naturally occurring brain chemical.[citation needed] 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 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. This is an important physiological pathway for the medical treatment of pain.

Sustainability in the body Main article: Cannabis drug testing

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; heavy users can produce positive tests for up to 3 months after ceasing cannabis use (see drug test).

Toxicity

No fatal overdoses with cannabis use have been reported as of 2010. A review published in the British Journal of Psychiatry in February 2001 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 lab animal tests, scientists have had much difficulty administering a dosage of THC that is high enough to be lethal.

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.

The ratio of cannabis material required to produce a fatal overdose to the amount required to saturate cannabinoid receptors and cause intoxication is approximately 40,000:1. It was found in 2007 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).[non-primary source needed] 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.[non-primary source needed] Mainstream cannabis smoke was found to contain higher concentrations of selected polycyclic aromatic hydrocarbons (PAHs) than sidestream tobacco smoke.[non-primary source needed] 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.[30] 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 due to prolonged, repeated use and the development of a tolerance to cannabinoids.

Psychoactive effects

See also: Medical cannabis

The psychoactive effects of cannabis, known as a "high", are subjective and can vary based on the person 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 humor, music (especially discerning its various components/instruments) or the arts, 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.

Cannabis also produces many subjective and highly tangible effects, such as greater enjoyment of food taste and aroma, an enhanced enjoyment of music and comedy, and marked distortions in the perception of time and space (where experiencing a "rush" of ideas from the bank of long-term memory can create the subjective impression of long elapsed time, while a clock reveals that only a short time has passed). At higher doses, effects can include altered body image, auditory and/or visual illusions, pseudo-hallucinatory, and ataxia from selective impairment of polysynaptic reflexes. In some cases, cannabis can lead to dissociative states such as depersonalization and derealization; such effects are most often considered desirable, but have the potential to induce panic attacks, critical introspection and paranoia in some unaccustomed users.[citation needed]

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.[40] If the episode is accompanied by aggression, sedation or physical restraint may be necessary.[40]

While many psychoactive drugs clearly fall into the category of either stimulant, depressant, or hallucinogen, cannabis exhibits a mix of all properties, perhaps leaning the most towards hallucinogenic or psychedelic properties, though with other effects quite pronounced as well. THC is typically considered the primary active component of the cannabis plant; various scientific studies have suggested that certain 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.

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

Effects of cannabis generally range from 10 minutes to 8 hours, depending on the potency of the dose, other drugs consumed, route of administration, set, setting, and personal tolerance to the drug's various effects.[citation needed] Smoked

The total short-term duration of cannabis use when smoked is based on the potency and how much is smoked. Effects can typically last two to three hours.

A Dutch double blind, randomized, placebo-controlled, cross-over study examining male volunteers aged 18–45 years with a self-reported history of regular cannabis use concluded that smoking of cannabis with very high THC levels (marijuana with 9–23% THC), as currently sold in coffee shops in the Netherlands, may lead to higher THC blood-serum concentrations. This is reflected by an increase of the occurrence of impaired psychomotor skills, particularly among younger or inexperienced cannabis smokers, who do not always adapt their smoking-style to the higher THC content. High THC concentrations in cannabis were associated with a dose-related increase of physical effects (such as increase of heart rate, and decrease of blood pressure) and psychomotor effects (such as reacting more slowly, decreased ability to focus and concentrate, making more mistakes during performance testing, having less motor control, and experiencing drowsiness).It was also observed during the study that the effects from a single joint lasted for more than eight hours. Reaction times remained impaired five hours after smoking, when the THC serum concentrations were significantly reduced, but still present. Also, when subjects smoke on several occasions per day, accumulation of THC in blood-serum may occur.

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 4–10 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 prevalently located 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.

Most notably, the two areas of motor control and memory are where the effects of cannabis are directly and irrefutably evident.[citation needed] Cannabinoids, depending on the dose, inhibit the transmission of neural signals through the basal ganglia and cerebellum. At lower doses, cannabinoids seem to stimulate locomotion while greater doses inhibit it, most commonly manifested by lack of steadiness (body sway and hand steadiness) in motor tasks that require a lot of attention. Other brain regions, like the cortex, the cerebellum, and the neural pathway from cortex to striatum, are also involved in the control of movement and contain abundant cannabinoid receptors, indicating their possible involvement as well.

Experiments on animal and human tissue have demonstrated a disruption of short-term memory formation, which is consistent with the abundance of CB1 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 major decrease in neuronal activity in that region. This decrease in activity resembles a "temporary hippocampal lesion."

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.[50] Effects on driving

Cannabis usage has been shown 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 "Cannabis impairs driving behaviour. However, this impairment is mediated in that subjects under cannabis treatment appear to perceive that they are indeed impaired. Where they can compensate, they do, for example ... effects of driving behaviour are present up to an hour after smoking but do not continue for extended periods". The report summarizes current knowledge about the effects of cannabis on driving and accident risk based on a review of available literature published since 1994 and the effects of cannabis on laboratory based tasks. The study identified young males, amongst whom cannabis consumption is frequent and increasing, and in whom alcohol consumption is also common, as a risk group for traffic accidents. The cause, according to the report, is driving inexperience and factors associated with youth relating to risk taking, delinquency and motivation. These demographic and psychosocial variables may relate to both drug use and accident risk, thereby presenting an artificial relationship between use of drugs and accident involvement.

Kelly, Darke and Ross show similar results, with laboratory studies examining the effects of cannabis on skills utilised while driving showing impairments in tracking, attention, reaction time, short-term memory, hand-eye coordination, vigilance, time and distance perception, and decision making and concentration. An EMCDDA review concluded that "the acute effect of moderate or higher doses of cannabis impairs the skills related to safe driving and injury risk", specifically "attention, tracking and psychomotor skills". In their review of driving simulator studies, Kelly et al. conclude that there is evidence of dose-dependent impairments in cannabis-affected drivers' ability to control a vehicle in the areas of steering, headway control, speed variability, car following, reaction time and lane positioning. The 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. The estimated fatal crash odds for cannabis (1.26) were lower than: opiates (1.68), antianxiety medications (2.30), zopiclone (sleep medicine) (2.60), cocaine (2.96), and amphetamines (5.17). The estimated injury odds for cannabis (1.10) were lower than: antihistamines (1.12), penicillin (1.12), antianxiety meds (1.17), antidepressants (1.35), antiasthmatics (1.31), zopiclone (sleep medicine) (1.42), cocaine (1.66), and opiates (1.91). The study concluded: "By and large, the increase in the risk of accident involvement associated with the use of drugs must be regarded as modest...Compared to the huge increase in accident risk associated with alcohol, as well as the high accident rate among young drivers, the increases in risk associated with the use of drugs are surprisingly small."

A report from the University of Colorado, Montana State University, and the University of Oregon found that on average, states that have legalized Medical cannabis had a decrease in traffic-related fatalities by 8-11%. The researchers hypothesized "it’s just safer to drive under the influence of marijuana than it is drunk....Drunk drivers take more risk, they tend to go faster. They don’t realize how impaired they are. People who are under the influence of marijuana drive slower, they don’t take as many risks”. Another consideration, they added, was the fact that users of marijuana tend not to go out as much.[60] 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 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. This may be a result of raised carboxyhemoglobin levels from carbon monoxide. A similar increase in heart disease and ischemic strokes is observed in tobacco smokers, which suggests that the harmful effects come from a variety of combustion products, not just marijuana.[citation needed]

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.[70] However, all of the cases also involved tobacco[citation needed] (a known cause of Buerger's disease) in one way or another, and nearly all of the cannabis use was quite heavy .[citation needed] Combination with other drugs

The most obvious 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. Memory and learning Main article: Cannabis and memory

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”.[80] 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 popular American and United Kingdom culture. Clinical studies and survey data have found that cannabis increases food enjoyment and interest in food. Scientists have claimed to be able to explain what causes the increase in appetite, concluding that "endocannabinoids in the hypothalamus activate cannabinoid receptors that are responsible for maintaining food intake". 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 were also found in human breast milk.[90] 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.[citation needed] Some of the microorganisms found create aflatoxins, which are toxic and carcinogenic. Researchers suggest that moldy cannabis thus be discarded.[citation needed]

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 Main articles: Long-term effects of cannabis and Cannabis dependence

Exposure to marijuana has 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, and vasculature" according to a 2013 literature review by Gordon and colleagues.

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 cannabis withdrawal. Such drugs include bupropion, divalproex, nefazodone, lofexidine, and dronabinol. Of these, dronabinol has proven the most effective. Effects in pregnancy Main article: Cannabis in pregnancy

Cannabis consumption in pregnancy is associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits in offspring. 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.