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Institute of medication (US); happiness JE, Watson SJ Jr., Benson JA Jr., editors. Marijuana and also Medicine: Assessing the scientific research Base. Washington (DC): national Academies press (US); 1999.


Primum no nocere. This is the physician"s an initial rule: whatever treatment a doctor prescribes come a patient—first, the treatment need to not injury the patient.

The most contentious element of the clinical marijuana conflict is no whether marijuana have the right to alleviate particular symptoms but rather the degree of harm associated with its use. This thing explores the an unfavorable health consequences of marijuana use, first with respect to drug abuse, then from a psychological perspective, and finally native a physiological perspective.


The most typically reported effects of exhilaration marijuana room a sense of health or euphoria and increased talkativeness and laughter alternative with periods of introspective dreaminess adhered to by lethargy and also sleepiness (see evaluate by Adams and also Martin, 1996,1 Hall and also Solowij,59 and Hall et al. 60). A characteristic feature of a marijuana “high” is a distortion in the feeling of time associated with deficits in temporary memory and also learning. A marijuana smoker typically has a feeling of intensified physical and also emotional sensitivity, including a emotion of higher interpersonal closeness. The most evident behavioral abnormality displayed by who under the influence of marijuana is challenge in delivering on an easy to understand conversation, perhaps since of an inability to mental what was simply said even a few words earlier.

The high connected with marijuana is not generally claimed to be integral come its therapeutic value. But mood enhancement, tension reduction, and mild sedation have the right to be desirable qualities in medications—par-ticularly for patients enduring pain and anxiety. Thus, although the psychological impacts of marijuana are simply side results in the therapy of part symptoms, castle might contribute directly come relief of various other symptoms. They likewise must be monitored in managed clinical trials come discern which effect of cannabinoids is beneficial. These possibilities are questioned later under the discussions of certain symptoms in chapter 4.

The effects of miscellaneous doses and also routes of shipment of THC are displayed in Table 3.1.



Psychoactive doses of THC in Humans.

Adverse the atmosphere Reactions

Although euphoria is the more common reaction to cigarette smoking marijuana, disadvantage mood reactions deserve to occur. Such reactions occur most frequently in inexperienced users after huge doses of exhilaration or oral marijuana. They generally disappear within hours and also respond fine to reassurance and a donate environment. Anxiety and paranoia room the most common acute adverse reactions;59 others include panic, depression, dysphoria, depersonalization, delusions, illusions, and hallucinations.1,40,66,69 Of continual marijuana smokers, 17% report the they have actually experienced at the very least one the the symptoms, usually early on in their usage of marijuana.145 Those observations are an especially relevant for the usage of medical marijuana in civilization who have actually not previously provided marijuana.


There are countless misunderstandings around drug abuse and also dependence (see reviews by O"Brien114 and also Goldstein54). The terms and concepts used in this report space as identified in the most recent Diagnostic and also Statistical hand-operated of psychological Disorders (DSM-IV ),3 the most significant system in the United claims for diagnoses of psychological disorders, consisting of substance abuse (see crate 3.1). Tolerance, dependence, and withdrawal are often presumed to imply abuse or addiction, however this is no the case. Tolerance and also dependence room normal physiological adaptations to repetitive use of any kind of drug. The correct use of prescribed drugs for pain, anxiety, and even hypertension frequently produces tolerance and also some measure of physiological dependence.

Box 3.1

Definitions. Addiction. Problem dependence. Craving refers to the intense desire because that a drug and is the most challenging aspect of seeks to overcome.

Even a patient that takes a medicine for proper medical indications and at the correct dosage can develop tolerance, physics dependence, and withdrawal symptoms if the medicine is stopped abruptly rather than gradually. Because that example, a hypertensive patient receiving a beta-adrenergic receptor blocker, such as propranolol, could have a good therapeutic response; but if the medicine is quit abruptly, there can be a withdrawal syndrome that is composed of tachycardia and a rebound rise in blood pressure to a allude that is temporarily greater than before administration of the medication began.

Because that is an illegal substance, some civilization consider any type of use that marijuana together substance abuse. However, this report provides the medical definition; that is, problem abuse is a maladaptive sample of recurring substance use manifested by recurrent and far-reaching adverse consequences.3 substance abuse and dependence space both diagnoses the pathological substance use. Dependency is the much more serious diagnosis and implies compulsive drug use that is challenging to prevent despite far-reaching substance-related problems (see box 3.2).

Box 3.2

DSM-IV Criteria for Substance Dependence. A maladaptive pattern of substance use, resulting in clinically significant impairment or distress, as manifested by three (or more) the the following, developing at any type of time in the exact same 12-month period: Tolerance, (more...)


Drugs vary in their capacity to produce good feelings in users, and the more strongly reinforcing a medicine is, the more likely it will be abused (G. Koob, academy of medicine (IOM) workshop). Marijuana is indisputably reinforcing for numerous people. The reinforcing properties of also so gentle a stimulant together caffeine are usual of reinforcement by addicting drugs (reviewed by Goldstein54 in 1994). Caffeine is reinforcing for many human being at low doses (100–200 mg, the mean amount of caffeine in one to 2 cups the coffee) and is aversive at high sheep (600 mg, the mean amount of caffeine in six cups of coffee). The reinforcing effects of many drugs are different for various people. For example, caffeine was most reinforcing because that test topics who scored lowest on test of anxiety but tended no to be reinforcing because that the many anxious subjects.

As an debate to dispute the abuse potential that marijuana, some have actually cited the monitoring that pets do not willingly self-administer THC, together they will certainly cocaine. Also if the were true, it would certainly not be pertinent to human being use that marijuana. The value in animal models of medicine self-administration is not that lock are crucial to display that a drug is reinforcing however rather that they provide a model in which the impacts of a drug deserve to be studied. Furthermore, THC is indeed rewarding to pets at part doses but, like numerous reinforcing drugs, is aversive in ~ high doses (4.0 mg/ kg).93 similar effects have been found in experiments conducted in animals outfitted through intravenous catheters that permit them to self-administer win 55,212, a medicine that mimics the results of THC.100

A specific set of neural pathways has actually been suggest to it is in a “reward system” that underlies the combine of drugs of abuse and other pleasurable stimuli.51 Reinforcing nature of medicine are linked with their capability to boost concentrations of specific neurotransmitters in locations that are component of the proposed mind reward system. The average forebrain bundle and the cell core accumbens are linked with brain reward path-ways.88 Cocaine, amphetamine, alcohol, opioids, nicotine, and also THC144 all rise extracellular liquid dopamine in the nucleus accumbens an ar (reviewed by Koob and Le Moal88 and Nestler and also Aghajanian110 in 1997). However, the is crucial to keep in mind that brain reward systems room not strictly “drug combine centers.” Rather, their biological role is come respond to a range of optimistic stimuli, consisting of sweet foods and sexual attraction.


The price at which yongin to the various results of any drug develops is an essential consideration because that its safety and efficacy. For clinical use, yongin to some effects of cannabinoids can be desirable. Differences in the rates at which tolerance to the multiple impacts of a drug establishes can it is in dangerous. For example, yongin to the euphoric effects of heroin develops faster than tolerance to its respiratory depressant effects, for this reason heroin users tend to boost their daily doses to reach their desired level that euphoria, thereby putting themselves at threat for respiratory arrest. Due to the fact that tolerance to the various impacts of cannabinoids might build at various rates, it is vital to evaluate individually their results on mood, motor performance, memory, and also attention, as well as any therapeutic usage under investigation.

Tolerance to most of the results of marijuana can construct rapidly after just a few doses, and it additionally disappears rapidly. Yongin to huge doses has been discovered to persist in experimental animals for lengthy periods after cessation of drug use. Performance special needs is less among people who usage marijuana greatly than it is amongst those who use marijuana only occasionally,29,104,124 possibly due to the fact that of tolerance. Heavy users tend to reach higher plasma concentrations of THC than light customers after similar doses the THC, arguing against the opportunity that hefty users present less power impairment because they in which method absorb less THC (perhaps early to differences in smoking behavior).95

There show up to be variations in the development of tolerance to the various effects the marijuana and oral THC. For example, everyday marijuana smokers participated in a residential laboratory examine to to compare the breakthrough of tolerance to THC pills and also to acting marijuana.61,62 One team was offered marijuana cigarettes to smoke four times per day for 4 consecutive days; one more group was offered THC pills ~ above the exact same schedule. Throughout the four-day period, both groups became tolerant to feeling “high” and also what castle reported as a “good drug effect.” In contrast, no group ended up being tolerant to the stimulatory impacts of marijuana or THC on appetite. “Tolerance” walk not median that the medicine no longer developed the effects but simply the the impacts were much less at the finish than in ~ the beginning of the four-day period. The marijuana smoking group reported emotion “mellow” after ~ smoking and also did not present tolerance to this effect; the team that took THC pills did not report emotion “mellow.” The distinction was also reported by many human being who explained their experiences to the IOM examine team.

The oral and smoked doses to be designed to deliver around equivalent quantities of THC to a subject. Each smoked marijuana dose contained five 10-second puffs of a marijuana cigarette containing 3.1% THC; the pills included 30 mg of THC. Both groups also received placebo drugs throughout other four-day periods. Although the dosing that the two groups was comparable, various routes of management resulted in different patterns of medicine effect. The peak effect of exhilaration marijuana is usually felt within minutes and declines sharply after 30 minutes68,95; the peak impact of dental THC is commonly not felt until around an hour and also lasts for number of hours.118


A distinctive marijuana and also THC withdrawal syndrome has actually been identified, but it is mild and subtle contrasted with the profound physical syndrome of alcohol or heroin withdrawal.31,74 The symptoms of marijuana withdrawal include restlessness, irritability, soft agitation, insomnia, sleep EEG disturbance, nausea, and also cramping (Table 3.2). In addition to those symptoms, two recent studies detailed several more. A group of adolescents under therapy for command disorders additionally reported fatigue and illusions or hallucinations after marijuana abstinence (this research is discussed further in the section on “Prevalence and Predictors of dependence on Marijuana and Other Drugs”).31 In a residential study of day-to-day marijuana users, tap the money symptoms had sweating and runny nose, in enhancement to those detailed above.62 A marijuana withdrawal syndrome, however, has actually been reported just in a group of teenagers in therapy for substance abuse problems31 and in a research setup where topics were offered marijuana or THC daily.62,74


Withdrawal symptoms have actually been observed in very closely controlled laboratory researches of people after usage of both oral THC and smoked marijuana.61,62 In one study, topics were given very high sheep of oral THC: 180–210 mg every day for 10–20 days, roughly equivalent to smoking 9–10 2% THC cigarettes per day.74 during the abstinence duration at the finish of the study, the examine subjects to be irritable and also showed insomnia, runny nose, sweating, and also decreased appetite. The tap the money symptoms, however, were brief lived. In 4 days they had abated. The time course contrasts through that in an additional study in which lower doses of dental THC were provided (80–120 mg/day for four days) and withdrawal symptoms to be still near maximal after four days.61,62

In animals, simply discontinuing chronic heavy dosing the THC walk not reveal withdrawal symptoms, however the “removal” the THC from the mind can be made abrupt by one more drug that blocks THC in ~ its receptor if administered as soon as the chronic THC is withdrawn. The withdrawal syndrome is pronounced, and also the actions of the animals becomes hyperactive and disorganized.153 The half-life the THC in mind is around an hour.16,24 although traces of THC have the right to remain in the brain for much longer periods, the quantities are no physiologically significant. Thus, the lack of a tap the money syndrome as soon as THC is abruptly withdrawn without management of a receptor-blocking medicine is more than likely not due to a prolonged decline in mind concentrations.


Craving, the intense desire for a drug, is the most daunting aspect of seeks to overcome. Research study on craving has concentrated on nicotine, alcohol, cocaine, and opiates yet has not especially addressed marijuana.115 Thus, when this ar briefly evaluate what is known about drug craving, its relationship to marijuana use has actually not been established.

Most world who experience from seeks relapse within a year that abstinence, and they often attribute their relapse to craving.58 as addiction develops, craving increases also as maladaptive aftermath accumulate. Pet studies show that the propensity to relapse is based on changes in brain function that continue for months or years after the last usage of the drug.115 whether neurobiological conditions change during the manifestation of one abstinence syndrome remains an unanswered inquiry in medicine abuse research.88 The “liking” the sweet foods, because that example, is mediated through opioid forebrain systems and by brain stem systems, conversely, “wanting” seems to be mediated through ascending dopamine neurons that job to the cell core accumbens.109

Anticraving medications have been arisen for nicotine and alcohol. The antidepressant, bupropion, blocks nicotine craving, while naltrexone blocks alcohol craving.115 another category of addiction medication contains drugs the block various other drugs" effects. Few of those drugs likewise block craving. For example, methadone block the euphoric effects of heroin and additionally reduces craving.

Prevalence the Use

Millions that Americans have tried marijuana, yet most room not regular users. In 1996, 68.6 million people—32% that the U.S. Population over 12 year old—had do the efforts marijuana or hashish at the very least once in your lifetime, however only 5% were present users.132 Marijuana usage is most prevalent amongst 18- come 25-year-olds and declines high solution after the period of 34 (Figure 3.1).77,132 whites are an ext likely than blacks to usage marijuana in adolescence, although the distinction decreases through adulthood.132

Most civilization who have actually used marijuana walk so first during adolescence. Society influences, such as peer pressure and prevalence of use by peers, are highly predictive of initiation right into marijuana use.9 Initiation is not, of course, associated with ongoing or constant use. A cohort the 456 students who experimented through marijuana throughout their high school years were surveyed around their reasons for initiating, continuing, and also stopping your marijuana use.9 students who began as heavy users were excluded native the analysis. Those that did not become regular marijuana users cited two varieties of factors for discontinuing. The an initial was regarded health and well-being; the is, castle felt that marijuana was bad for their wellness or for your family and work relationships. The second kind was based on age-related transforms in circumstances, consisting of increased responsibility and also decreased regular call with other marijuana users. Amongst high college students that quit, parental disapproval to be a stronger affect than peer not say in discontinuing marijuana use. In the initiation of marijuana use, the reverse was true. The factors cited by those who ongoing to use marijuana to be to “get in a far better mood or feel better.” Social factors were no a significant predictor of continued use. Data ~ above young adults show comparable trends. Those who usage drugs in solution to social influences are an ext likely to protect against using them than those who also use castle for emotional reasons.80

The age distribution of marijuana users amongst the general population contrasts v that of clinical marijuana users. Marijuana usage generally decreases sharply after the age of 34 years, whereas clinical marijuana users often tend to more than 35. That raises the inquiry of what, if any, partnership exists in between abuse and also medical use of marijuana; however, no research studies reported in the scientific literature have addressed this question.

Prevalence and also Predictors of dependency on Marijuana and also Other Drugs

Many determinants influence the likelihood the a certain person will come to be a medicine abuser or an addict; the user, the environment, and also the drug room all important determinants (Table 3.3).114 The first two categories apply to potential abuse of any substance; the is, people who are delicate to drug abuse because that individual reasons and who find themselves in an setting that encourages drug abuse are initially likely come abuse the many readily accessible drug—regardless that its unique collection of impacts on the brain. The 3rd category consists of drug-specific impacts that influence the abuse liability of a details drug. As disputed earlier in this chapter, the an ext strongly reinforcing a medicine is, the an ext likely that it will be abused. The abuse legal responsibility of a drug is amplified by how quickly its impacts are felt, and also this is figured out by exactly how the medicine is delivered. In general, the impacts of medicine that space inhaled or injected space felt within minutes, and also the impacts of drugs that are ingested take a half hour or more.

The ratio of world who come to be addicted varies among drugs. Table 3.4 shows approximates for the proportion of people among the general population who used or came to be dependent top top different types of drugs. The ratio of individuals that ever ended up being dependent includes anyone that was ever before dependent—whether it to be for a period of weeks or years—and for this reason includes an ext than those who are right now dependent. Contrasted to most other drugs noted in this table, dependence amongst marijuana users is relatively rare. This could be early out to differences in specific drug effects, the availability of or penalties connected with the use of the various drugs, or some combination.

Daily usage of many illicit drugs is extremely rare in the basic population. In 1989, day-to-day use of marijuana among high college seniors was less than the of alcohol (2.9% and also 4.2%, respectively).76

Drug dependence is more prevalent in some sectors the the populace than in others. Age, gender, and also race or ethnic group are every important.8 not included tobacco and alcohol, the adhering to trends of drug dependence are statistically significant:8 men are 1.6 times as likely than ladies to come to be drug dependent, non-Hispanic white skin - man are about twice as likely as blacks to become drug dependent (the difference between non-Hispanic and Hispanic white skin - man was not significant), and people 25–44 years old are much more than three times as likely as those end 45 years old to become drug dependent.

More regularly than not, drug dependence co-occurs with various other psychiatric disorders. Most people with a diagnosis of drug dependence disorder also have a diagnosis of a an additional psychiatric disorder (76% the men and also 65% that women).76 The most frequent co-occurring disorder is alcohol abuse; 60% that men and also 30% of women with a diagnosis of medicine dependence additionally abuse alcohol. In females who space drug dependent, phobic disorders and major depression are practically equally typical (29% and 28%, respectively). Keep in mind that this study identified only between alcohol, nicotine and also “other drugs”; marijuana to be grouped amongst “other drugs.” The frequency v which drug dependence and also other psychiatric obstacle co-occur might not it is in the same for marijuana and other drugs that were consisted of in the category.

A strong association between drug dependence and also antisocial personality or the precursor, command disorder, is also widely report in children and adults (reviewed in 1998 by Robins126). Back the causes of the association room uncertain, Robins freshly concluded that it is more likely the conduct disorders normally lead to problem abuse 보다 the reverse.126 together a trend might, however, depend on the period at i beg your pardon the command disorder is manifested.

A longitudinal research by Brooks and co-workers provided a far-reaching relationship between adolescent drug use and disruptive disorders in young adulthood; except for previously psychopathology, such as childhood conduct disorder, the medicine use preceded the psychiatric disorders.18 In contrast with use of other illicit drugs and also tobacco, moderate (less than once a main and much more than once a month) to heavy marijuana use did not predict stress and anxiety or depressive disorders; however it was comparable to those various other drugs in predicting antisocial personality disorder. The rates of disruptive disorders increased with enhanced drug use. Thus, hefty drug usage among adolescents can be a warning authorize for later on psychiatric disorders; whether it is very early manifestation the or a cause of those disorders continues to be to be determined.

Psychiatric disorders are much more prevalent among teenagers who usage drugs—including alcohol and also nicotine—than among those who do not.79Table 3.5 shows that adolescent boys who smoke cigarettes day-to-day are around 10 times as likely to have a psychiatric disorder diagnosis together those who carry out not smoke. However, the table does not compare strongness of use among the various drug classes. Thus, although day-to-day cigarette smoking amongst adolescent boys is much more strongly linked with psychiatric disorders than is any use of illegal substances, the does not follow that this compare is true because that every quantity of tobacco smoking.79


Relative ubiquity of Diagnoses the Psychiatric Disorders connected with medicine Use amongst Children.

Few marijuana users end up being dependent on the (Table 3.4), however those who do encounter problems similar to those associated with dependence on other drugs.19,143 Dependence appears to be less severe among people that use just marijuana than amongst those that abuse cocaine or those who abuse marijuana with other drugs (including alcohol).19,143

Data gathered in 1990–1992 from the national Comorbidity examine of over 8,000 people 15–54 years old suggest that 4.2% of the general populace were dependent on marijuana at part time.8 similar results because that the frequency of problem abuse amongst the general population were obtained from the Epidemiological Catchment Area Program, a survey of end 19,000 people. Follow to data accumulated in the at an early stage 1980s for the study, 4.4% of adult have, in ~ one time, met the criteria for marijuana dependence. In comparison, 13.8% of adult met the criteria because that alcohol dependence and also 36.0% for tobacco dependence. After ~ alcohol and nicotine, marijuana to be the substance most frequently associated with a diagnosis of substance dependence.

In a 15-year study begun in 1979, 7.3% of 1,201 adolescents and young adults in suburban new Jersey at some time met the criteria because that marijuana dependence; this indicates that the price of marijuana dependence might be even higher in some teams of teenagers and young adults 보다 in the basic population.71 teenagers meet the criteria for medicine dependence at reduced rates that marijuana usage than carry out adults, and also this suggests that lock are much more vulnerable to dependence 보다 adults25 (see box 3.2).

Youths who are currently dependent on various other substances are an especially vulnerable come marijuana dependence. Because that example, Crowley and co-workers31 interviewed a group of 229 adolescent patient in a residential treatment regimen for delinquent, substance-involved youth and found that those patients were dependent top top an median of 3.2 substances. The teens had previously been diagnosed as dependent ~ above at the very least one problem (including nicotine and alcohol) and also had 3 or more conduct disorder symptoms during their life. Around 83% that those who had used marijuana at the very least six time went top top to build marijuana dependence. About equal number of youths in the study had a diagnosis the marijuana dependence and a diagnosis that alcohol dependence; fewer to be nicotine dependent. Comparisons of dependency potential in between different drugs have to be do cautiously. The probability that a details drug will be abused is affected by countless factors, consisting of the details drug results and access of the drug.

Although parents frequently state that marijuana brought about their youngsters to it is in rebellious, the troubled adolescents in the study by Crowley and also co-workers arisen conduct disorders before marijuana abuse. The is consistent with reports the the much more symptoms of command disorders youngsters have, the younger they start drug abuse,127 and that the previously they begin drug use, the an ext likely the is come be complied with by abuse or dependence.125

Genetic components are known to beat a duty in the likelihood the abuse because that drugs various other than marijuana,7,129 and it is not unexpected that genetic determinants play a duty in the marijuana experience, consisting of the likelihood the abuse. A research of end 8,000 male twins noted in the Vietnam Era twin Registry suggested that genes have actually a statistically far-ranging influence on whether a human finds the impacts of marijuana pleasant.97 not surprisingly, human being who discovered marijuana to it is in pleasurable supplied it an ext often than those who discovered it unpleasant. The study said that, return social impacts play crucial role in the initiation that use, individual differences—perhaps connected with the brain"s price system—influence whether a person will continue using marijuana. Similar results were found in a examine of woman twins.86 Family and also social environment strongly affected the likelihood of ever before using marijuana however had tiny effect top top the likelihood of heavy use or abuse. The last were more influenced by hereditary factors. Those outcomes are consistent with the finding the the level to i beg your pardon rats uncover THC lucrative is gene based.92

In summary, although couple of marijuana users develop dependence, some do. However they appear to be much less likely to perform so than users of other drugs (including alcohol and also nicotine), and also marijuana dependence shows up to be much less severe than dependence on various other drugs. Drug dependence is much more prevalent in some sectors that the population than others, however no team has been identified as specifically vulnerable come the drug-specific impacts of marijuana. Adolescents, particularly troubled ones, and people through psychiatric disorders (including problem abuse) show up to be much more likely 보다 the general population to end up being dependent ~ above marijuana.

See more: List Three Clues That Indicate That A Chemical Change Has Taken Place.

If marijuana or cannabinoid drugs were approved for therapeutic uses, it would certainly be necessary to consider the opportunity of dependence, particularly for patient at high risk for problem dependence. Some controlled substances that room approved medications produce dependence after permanent use; this, however, is a normal component of patience management and also does not generally present undue threat to the patient.