This in particular is a good link
https://www.ukcia.org/research/Pharm/index.php
Some of the most outstanding info from that link
ACTIONS OF CANNABIS IN HUMANS
Cannabis affects almost every body system. It combines many of the properties of alcohol, tranquillisers, opiates and hallucinogens; it is anxiolytic, sedative, analgesic, psychedelic; it stimulates appetite and has many systemic effects. In addition, its acute toxicity is extremely low: no deaths directly due to acute cannabis use have ever been reported. Only a selection of cannabis effects are described in this review; other actions are reviewed by Paton & Pertwee (1973), Pertwee (1995), Adams & Martin (1996) and many others.
Psychological effects
Effect on mood
The main feature of the recreational use of cannabis is that it produces a euphoriant effect or 'high'. The high can be induced with doses of THC as low as 2.5 mg in a herbal cigarette and includes a feeling of intoxication, with decreased anxiety, alertness, depression and tension and increased sociability (if taken in friendly surroundings). The high comes on within minutes of smoking and then reaches a plateau lasting 2 hours or more, depending on dose. It is not surprising that the overwhelming reason for taking cannabis given by recreational users is simply 'pleasure' (Webb et al, 1996, 1998). However, cannabis can also produce dysphoric reactions, including severe anxiety and panic, paranoia and psychosis. These reactions are dose-related and more common in naïve users, anxious subjects and psychologically vulnerable individuals. (Psychiatric reactions including aggravation or precipitation of schizophrenia are described by Johns, 2001, this issue).
Effects on perception
Accompanying the high, and often contributing to it, cannabis produces perceptual changes. Colours may seem brighter, music more vivid, emotions more poignant and meaningful. Spatial perception is distorted and time perception is impaired so that perceived time goes faster than clock time. Hallucinations may occur with high doses.
Effects on cognition and psychomotor performance
Not surprisingly, cannabis impairs cognitive and psychomotor performance. The effects are similar to those of alcohol and benzodiazepines and include slowing of reaction time, motor incoordination, specific defects in short-term memory, difficulty in concentration and particular impairment in complex tasks which require divided attention. The effects are dose-related but can be demonstrated after relatively small doses (5-10 mg THC in a joint), even in experienced cannabis users, and have been shown in many studies across a wide range of neurocognitive and psychomotor tests. These effects are additive with those of other central nervous system depressants.
Driving and piloting skills
These effects combine to affect skills related to driving a vehicle or flying an aeroplane. Numerous studies have shown that cannabis impairs road-driving performance and have linked cannabis use with increased incidence of road traffic accidents. In the UK, USA, Australia, New Zealand and many European countries, cannabis is the most common drug, apart from alcohol, to be detected in drivers involved in fatal accidents or stopped for impaired driving. A large proportion of such drivers have not taken alcohol or have concentrations below the legal limit. For example, in two studies from the UK Department of Transport (Everest et al, 1989; Department of Environment, Transport and the Regions, 1998), no alcohol was detected post-mortem in 70% and 80%, respectively, in road traffic accident fatalities testing positive for cannabis. In Australia (Road Safety Committee, 1995) only half of surviving drivers of vehicle collisions involving death or life-threatening injuries who tested positive for cannabis had also taken alcohol. In Norway, 56% of a sample of drug-impaired drivers negative for alcohol gave positive blood samples for THC (Gjerde & Kinn, 1991). From the USA, McBay (1986) had earlier found that 75% of a sample of drivers with cannabinoids in their blood were also intoxicated with alcohol. The World Health Organization (1997, p. 15) concluded:
"There is sufficient consistency and coherence from experimental studies and studies of cannabinoid levels among accident victims...to conclude that there is an increased risk of motor vehicle accidents among persons who drive when intoxicated with cannabis.... The risk is magnified when cannabis is combined with intoxicating doses of alcohol".
Piloting an aeroplane is an even more complex task than driving a car and cannabis has been shown in several investigations seriously to impair aircraft piloting skills. The results of one placebo-controlled study are shown in Fig. 4 (Leirer et al, 1991). The subjects were nine licensed pilots, highly trained in a flight simulator task, who were current cannabis users. They received a cannabis cigarette containing 20 mg THC (a moderate dose by present-day standards). This dose caused a significant decrement in performance compared with placebo and the impairment lasted over 24 hours after this single dose. Furthermore, most of the pilots were unaware that their performance was still impaired at 24 hours. Several pilots reported that they had actually flown while high on cannabis, and the authors noted that in at least one aeroplane crash the pilot was known to have taken cannabis some hours before flying and to have made a similar landing misjudgement (poor alignment on the runway) as was noted in experimental studies.
Fig. 4 Effect of smoking a cannabis cigarette containing 20 mg tetrahydrocannabinol (THC) on pilot performance in a flight simulator landing task (Leirer et al, 1991), [double dash, black square, double dash], 20 mg THC; [horizontal bar, black circle, horizontal bar], placebo.
There is evidence that similar longlasting impairments apply to motor cyclists, train drivers, signal operators, air traffic controllers and operators of heavy machinery. However, a problem is that because of the very slow elimination of cannabinoids, there is no accurate way of relating blood, urine, saliva or sweat concentrations to the degree of intoxication of the driver or pilot at the time of an accident, no way of telling exactly when the last dose was taken and no proof that cannabis was actually the cause of an accident.
Long-term effects of chronic use
There is considerable evidence, reviewed by Hall et al (1994), that performance in heavy, chronic cannabis users remains impaired even when they are not actually intoxicated. These impairments, especially of attention, memory and ability to process complex information, can last for many weeks, months or even years after cessation of cannabis use (Solowij, 1998). Whether or not there is permanent cognitive impairment in heavy long-term users is not clear.
Tolerance, dependence, withdrawal effects
Tolerance has been shown to develop to many effects of cannabis including the high and many systemic effects, and a cannabis withdrawal syndrome has been clearly demonstrated in controlled studies in both animals and man (Jones, 1983; Kouri et al, 1999). The withdrawal syndrome has similarities to alcohol, opiate and benzodiazepine withdrawal states and includes restlessness, insomnia, anxiety, increased aggression, anorexia, muscle tremor and autonomic effects. A daily oral dose of 180 mg of THC (one or two modern, good-quality joints) for 11-21 days is sufficient to produce a well-defined withdrawal syndrome (Jones, 1983). The development of tolerance leads some cannabis users to escalate dosage, and the presence of withdrawal syndrome encourages continued drug use. Thus, chronic cannabis use can lead to drug dependence, and reports from the USA, UK and New Zealand (Roffman & Barnhart, 1987; Stephens et al, 1993) indicate that many cannabis users are now seeking treatment for cannabis dependence.
Systemic effects
Cardiovascular effects
Cannabinoids produce a dose-related tachycardia which may reach rates of up to 160 beats/minute or more, although tolerance develops with chronic use. There is also a widespread vasodilation and reddening of the conjunctivae, a characteristic sign of cannabis use (Paton & Pertwee, 1973). Postural hypotension and fainting may occur. These and other cardiovascular effects may carry a risk for individuals with preexisting cardiac disease, and several cases of acute and sometimes fatal cardiac incidents have been reported in young cannabis smokers.
Effects on the respiratory system
The smoke from herbal cannabis preparations contains all the same constituents (apart from nicotine) as tobacco smoke, including carbon monoxide, bronchial irritants, tumour initiators (mutagens), tumour promoters and carcinogens (British Medical Association, 1997). The tar from a cannabis cigarette contains higher concentrations of benzanthracenes and benzpyrenes, both of which are carcinogens, than tobacco smoke. It has been estimated that smoking a cannabis cigarette results in approximately a fivefold greater increase in carboxyhaemoglobin concentration, a three-fold greater amount of tar inhaled and retention in the respiratory tract of one-third more tar than smoking a tobacco cigarette (Wu et al, 1988; Benson & Bentley, 1995). This is mainly due to the way a cannabis joint is smoked, with deep and prolonged inhalation and no filter. In addition, cannabis has a higher combustion temperature than tobacco.
Chronic cannabis smoking is associated with bronchitis and emphysema. It has been calculated that smoking 3-4 cannabis cigarettes a day is associated with the same evidence of acute and chronic bronchitis and the same degree of damage to the bronchial mucosa as 20 or more tobacco cigarettes a day (Benson & Bentley, 1995). Prospective studies of the long-term effects on the lungs of chronic cannabis smoking are lacking, but some authors suggest that chronic airways disease and bronchogenic carcinoma may be as great a risk as with tobacco smoking. In addition, there appears to be an increased incidence of rare forms of oropharyngeal cancer in young people who smoke cannabis chronically.
Effects on other systems
Cannabis also has immunosuppressant and endocrine effects although the clinical significance of these is still not clear. Chronic cannabis use appears to carry reproductive risks, both to the mother during pregnancy and childbirth and to the foetus and neonate, although these areas need further study. The full extent of long-term health risks of chronic cannabis use (if today's young smokers continue the habit) may require a latent period of 10-20 years to be revealed.
CLINICAL IMPLICATIONS
* Cannabis use is associated with increased risk of road, rail and air traffic accidents.
* Chronic cannabis use can result in tolerance, dependence, withdrawal effects and possibly long-term cognitive impairment.
* Long-term cannabis use carries respiratory, cardiovascular and other health risks.
LIMITATIONS
* There is no clear relationship between cannabinoid concentrations in body fluids and degree of psychomotor impairment, making traffic-control policies difficult.
* Long-term prospective controlled studies are needed to quantify the health risks of chronic cannabis use.
* Further research is needed on the effects of individual cannabinoids and their interactions with tetrahydrocannabinol.
REFERENCES
Adams, I. B. & Martin, B. R. (1996) Cannabis: pharmacology and toxicology in animals and humans. Addiction, 91, 1585-1614.[Context Link]
Agurell, S., Halldin, M., Lindgren, J.-E., et al (1986) Pharmacokinetics and metabolism of [DELTA]1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacological Reviews, 38, 21-43. [Context Link]
Benson, M. & Bentley, A. M. (1995) Lung disease induced by drug addiction. Thorax, 50, 1125-1127. [Context Link]
Birch, D., Ashton, H. & Kamali, F. (1998) Alcohol drinking, illicit drug use and stress in junior house officers in the north east of England Lancet, 352, 785-786. [Context Link]
British Medical Association (1997) Therapeutic Uses of Cannabis. London: Harwood Academic. [Context Link]
Department of Environment, Transport and the Regions (DETR) (1998) Report on Incidence of Drugs in Road Accident Victims: Interim. Results of Survey. January. London: Department of Transport Publications. [Context Link]
Devane, W.A., Dysarz, F.A., Johnson, M.R., et al (1988) Determination and characterisation of a cannabinoid receptor in rat brain. Molecular Pharmacology, 34, 605. [Context Link]
Devane, W.A., Hanus, L., Breuer, A., et al (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 258, 1946-1949. [Context Link]
Everest, J.T., Tunbridge, R. J. & Widdop, B. (1989) The Incidence of Drugs in Road Accident Fatalities. Department of Transport and Road Research Laboratory Research Report 202. London: Department of Transport Publications. [Context Link]
Gjerde, H. & Kinn, G. (1991) Impairment in drivers due to cannabis. Forensic Science International, 50, 57-60. [Context Link]
Gold, M. S. (1991) Marijuana, In Comprehensive Handbook of Alcohol and Drug Addiction (ed. N. S. Miller), pp. 353-376. New York: Marcel Decker. [Context Link]
Hall, W. & Solowij, N. (1998) Adverse effects of cannabis. Lancet, 352, 1611-1615.
Hall, W., Solowij, N. & Lemon, J. (1994) The Health and Social Consequences of Cannabis Use. National Drug Strategy Monograph Series No. 25. Canberra: Australian Government Publishing Service. [Context Link]
Herkenham, M. (1995) Localization of cannabinoid receptors in brain and periphery. In Cannabinoid Receptors (ed. R. Pertwee), pp. 145-166. London: Academic Press. [Context Link]
Johns, A. (2001) Psychiatric effects of cannabis. British Journal of Psychiatry, 178, 116-22. [Context Link]
Jones, R. T. (1983) Cannabis tolerance and dependence. In Cannabis and Health Hazards (eds K. O. Fehr & H. Kalant). Toronto: Addiction Research Foundation. [Context Link]
Kouri, E. M., Harrison, G., Pope, G. Jr., et al (1999) Changes in aggressive behavior during withdrawal from long-term marijuana use. Psychopharmacology, 143, 302-308. [Context Link]
Leirer, V. O., Yesavage, J. A. & Morrow, D. G. (1991) Marijuana carry-over effects on aircraft pilot performance. Aviation & Space Environmental Medicine, 62, 221-227. [Context Link]
Maykut, M. O. (1985) Health consequences of acute and chronic marijuana use. Progress in Neuropsychopharmacology and Biological Psychiatry, 9, 209-238. [Context Link]
McBay, A. J. (1986) Drug concentrations and traffic safety. Alcohol, Drugs and Driving, 2, 51-59. [Context Link]
Mendelson, J. H. (1987) Marijuana. In Psychopharmacology: The Third Generation of Progress (ed. H. Y. Meltzer), pp. 1565-1568. New York: Raven Press. [Context Link]
Miller, P. McC. & Plant, M. (1996) Drinking, smoking and illicit drug use among 15 and 16 year olds in the United Kingdom. British Medical Journal, 313, 394-397. [Context Link]
Munro, S., Thomas, K. L. & Abu-Shaar, M. (1993) Molecular characterization of peripheral receptor for cannabinoids. Nature, 365, 61-65. [Context Link]
Nahas, G. G. (1975) Marijuana: toxicity and tolerance. In Medical Aspects of Drug Abuse (ed. R. W. Richter), pp. 16-36. Baltimore, MD: Harper & Row. [Context Link]
Paton, W. D. M. & Pertwee, R. G. (1973) The actions of cannabis in man. In Marijuana: Chemistry, Pharmacology, Metabolism and Clinical Effects (ed. R. Mechoulam), pp. 288-334. London: Academic Press. [Context Link]
Pertwee, R. G. (1995) Pharmacological, physiological and clinical implications of the discovery of cannabinoid receptors: an overview. In Cannabinoid Receptors (ed. R. G. Pertwee), pp. 1-34. London: Academic Press. [Context Link]
Road Safety Committee (1995) Inquiry into the Effects of Drugs (other than Alcohol) on Road Safety in Victoria. Melbourne: L. V. North, Government Printer. [Context Link]
Robertson, J. R., Miller, P. & Anderson, R. (1996) Cannabis use in the community. British Journal of General Proctice, 46, 671-674.
Roffman, R. A. & Barnhart, R. (1987) Assessing need for marijuana dependence treatment through anonymous telephone interviews. International Journal of Addictions, 22, 639-651. [Context Link]
Schwartz, R. H. (1991) Heavy marijuana use and recent memory impairment. In Physiopathology of Illicit Drugs: Cannabis, Cocaine, Opiates (eds G. G. Nahas & C. Latour), pp. 13-21. Oxford: Pergamon Press. [Context Link]
Solowij, N. (1998) Cannabis and Cognitive Functioning. Cambridge: Cambridge University Press. [Context Link]
Stephens, R. S., Roffman, R. A. & Simpson, E. E. (1993) Adult marijuana users seeking treatment. Journal of Consulting and Clinical Psychology, 61, 1100-1104. [Context Link]
Tanda, G., Pontieri, F. E. & Di Chiara, G. (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common µ1 opioid receptor mechanism. Science, 276, 2048-2050. [Context Link]
Webb, E., Ashton, C. H., Kelly, P., et al (1996) Alcohol and drug use in UK university students. Lancet, 348, 922-925. [Context Link]
Webb, E., Ashton, C. H., Kelly, P., et al (1998) An update on British medical students' lifestyles. Medical Education, 32, 325-331. [Context Link]
World Health Organization (1997) Programme on Substance Abuse. Cannabis: A Health Perspective and Research Agenda. Geneva: WHO. [Context Link]
Wu, T.-C., Scott, R. T. A., Burnett, S. J., et al (1988) Pulmonary hazards of smoking marijuana as compared with tobacco. New England Journal of Medicine, 318, 347-351. [Context Link]
)
