Cannabis has both psychological and physiological effects on the human body. The effects of cannabis are caused by cannabinoids, most notably tetrahydrocannabinol (THC). Five European countries, Canada, and thirteen US states have legalized medical cannabis if prescribed for nausea, pain, and alleviation of symptoms surrounding chronic illness, although it remains banned, but decriminalized under US state law.
Acute effects while under the influence can include euphoria, anxiety, temporary short-term memory loss, and circulation effects which may increase risks of heart attacks and strokes. However, chronic use is not associated with some cardiovascular risk factors such as blood triglyceride levels and blood pressure, as indicated in a longitudinal study. The evidence of long-term effects on memory is preliminary and hindered by confounding factors. Concerns have been raised about the potential for long-term cannabis consumption to increase risk for schizophrenia, bipolar disorders, and major depression, but the ultimate conclusions on these factors are disputed.
The most prevalent psychoactive substances in cannabis are cannabinoids, including delta-9-tetrahydrocannabinol (Δ9-THC, commonly called simply 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.
THCV is not psychoactive in fact it is a THC antagonist. This was finally proven 5 years ago.
Thomas, A., Stevenson, L.A., Wease, K.N., Price, M.R., Baillie, G., Ross, R.A. and Pertwee, R.G. (2005) Evidence that the plant cannabinoid delta-9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. Br. J. Pharmacol. 146: 917-926.
Pertwee, R.G., Thomas, A., Stevenson, L.A., Ross, R.A., Varvel, S.A., Lichtman, A.H., Martin, B.R. and Razdan, R.K. (2007) The psychoactive plant cannabinoid, delta-9-tetrahydrocannabinol, is antagonized by delta-8- and delta-9-tetrahydrocannabivarin in mice in vivo. Br. J. Pharmacol. 150: 586-594.
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 sidechain, 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. Marijuana with relatively high ratios of THC:CBD is less likely to induce anxiety than marijuana with low THC:CBD ratios. 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.
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. Cannabinoids usually contain a 1,1'-di-methyl-pyrane 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. 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.
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 homology 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.
Most cannabinoids are lipophilic (fat soluble) compounds that easily store 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, after using cannabis depending on frequency of use (see drug test). This detection is possible because non-psychoactive THC metabolites are stored for long periods of time in fat cells, and THC has an extremely low water solubility. The rate of elimination of metabolites is slightly greater for more frequent users due to tolerance.
THC 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. It also appears that humans cannot die from ingesting too much THC, unless it were introduced into the body intravenously (See also: Intravenous Marijuana Syndrome). Indeed, a 1988 ruling from the United States Department of Justice concluded that "In practical terms, marijuana cannot induce a lethal response as a result of drug-related toxicity."
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 assumption 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; consumption of such a large dose is virtually impossible. It is generally considered impossible to overdose on marijuana, as the user would certainly either fall asleep or otherwise become incapacitated from the effects of the drug before being able to consume enough THC to be mortally toxic. Another commonly quoted reason is that the timeframe in which consumption would be fatal is at odds with the amount which must be consumed. According to a 2006 United Kingdom government report, using cannabis is much less dangerous than tobacco, prescription drugs, and alcohol in social harms, physical harm, and addiction. 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). This study found that directly inhaled cannabis smoke contained 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. Sidestream cannabis smoke was found to contain higher concentrations of selected polycyclic aromatic hydrocarbons (PAHs) than sidestream tobacco smoke.
Some of the short-term physical effects of cannabis use include increased heart rate, dry mouth (cotton mouth or peanut-butter mouth), reddening of the eyes (congestion of the conjunctival blood vessels), a reduction in intra-ocular pressure, muscle relaxation, a sensation of cold or hot hands and feet.
The psychoactive effects of cannabis, known as a "high", are subjective and can vary based on the individual and the method of use. Some effects may include an altered state of consciousness, euphoria, feelings of well-being, relaxation or stress reduction, increased appreciation of humor, music or art, joviality, metacognition and introspection, enhanced recollection (episodic memory), increased sensuality, increased awareness of sensation, increased libido, creative or philosophical thinking, disruption of linear memory and paranoia or anxiety.
Cannabis also produces many subjective 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 an up 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, and ataxia from selective impairment of polysynaptic reflexes. In some cases, cannabis can lead to depersonalization and derealization; such effects are most often considered undesirable.
Cannabis is biphasic in that at first it stimulates, then depresses, exactly how is dependent on the individual user, the Cannabinoid % content, and the Terpenoid content, as well as the amounts consumed, and how consumed, that is by eating, smoking, vaporizing, all of which modify the subjective effects. -David Watson CEO HortaPharm BV Amsterdam
Experiments on animal and human tissue have demonstrated disruption of short-term memory, 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, like 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 the end, this procedure could lead to the blocking of cellular processes that are associated with memory formation.
Cannabis consumption affects motor skills, reflexes, and attention, which is important when considering its effects on driving; however, this does not necessarily reflect impairment in terms of performance effectiveness, since few studies report increased accident risk.
Research in long-term effects of cannabis included analysis of reproductive effects, addiction potential, mental health, general health, in particular, cancer risk, behavioral effects, and effects on memory and intelligence, but none of this has been proven.
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 fungi and bacterial growth.
The fungi Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus parasiticus, Aspergillus tamarii, Aspergillus sulphureus, Aspergillus repens, Mucor hiemalis (not a human pathogen), Penicillin chrysogenum, Penicillin 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 thus be discarded.
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)."
In many countries, experimental science regarding cannabis is restricted due to its illegality. Thus, cannabis as a drug is often hard to fit into the structural confines of medical research because appropriate, research-grade samples are difficult to obtain for research purposes, unless granted under authority of national governments.
This issue was highlighted in the United States by the clash between Multidisciplinary Association for Psychedelic Studies (MAPS), an independent research group, and the National Institute on Drug Abuse (NIDA), a federal agency charged with the application of science to the study of drug abuse. The NIDA largely operates under the general control of the Office of National Drug Control Policy (ONDCP), a White House office responsible for the direct coordination of all legal, legislative, scientific, social and political aspects of federal drug control policy.
The cannabis that is available for research studies in the United States is grown at the University of Mississippi and solely controlled by the NIDA, which has veto power over the Food and Drug Administration (FDA) to define accepted protocols. Since 1942, when cannabis was removed from the U.S. Pharmacopoeia and its medical use was prohibited, there have been no legal (under federal law) privately funded cannabis production projects. This has resulted in a limited amount of research being done and possibly in NIDA producing cannabis which has been alleged to be of very low potency and inferior quality.
MAPS, in conjunction with Professor Lyle Craker, PhD, the director of the Medicinal Plant Program of the University of Massachusetts at Amherst, sought to provide independently grown cannabis of more appropriate research quality for FDA-approved research studies, and encountered opposition by NIDA, the ONDCP, and the U.S. Drug Enforcement Administration (DEA).
In countries such as the United Kingdom a license for growing cannabis is required if it is to be used for botanical or scientific reasons. It is referred to as a "controlled drug". In such countries a greater depth and variety of scientific research has been performed. Recently several habitual smokers were invited to partake in various tests by British medical companies in order for the UK government to ascertain the influence of cannabis on operating a motor vehicle.