Marijuana tolerance

The concept of tolerance is important in understanding the properties and effects of marijuana. Tolerance can be defined as the need for increasing doses of a drug over time to maintain the same effect achieved at previous lower doses. Receptors in the brain develop a tolerance to THC. Since the body becomes tolerant to the effects of marijuana, heavy users often feel a decreasing effect from the drug and thus may need to smoke ever-increasing quantities to achieve the earlier high. Because of this, we can see why tolerance is an important characteristic of dependence on marijuana. 

It is possible that iso-LSD may block LSD effects somewhat and inhibit the cosmic trips that can result from high doses this is however unproven. Nevertheless, the prime reasons for a lack of cosmicity are undoubtedly low doses and the development of tolerance. A single exposure to LSD or other psychedelics may produce an adaptation or tolerance that lasts the rest of your life (seeing the ocean for the first time is not a repeatable experience). Furthermore, as seems to be the case with the active chemical (THC) and its inhibitor (CBD) in marijuana, the presence of the inhibitor may sometimes result in a more pleasant experience. Only careful studies in which varying amounts of iso-LSD are added to LSD will decide the issue. 

In contrast, some drugs of abnse prodnce intense craving and are highly addictive bnt do not prodnce physical dependence. The absence of physical dependence indicates the relative lack of physiological withdrawal. This is not synonymous with meaning that discontinuation of these componnds may not be psychologically nncomfortable. Two examples are marijnana and cocaine. One need only look to the recent crack epidemic to see evidence of the way these substances can destroy lives, bnt they do not produce tolerance or risk of withdrawal to the same extent as alcohol or heroin. As a result, we would say that the daily crack or marijuana user meets the dehnition of substance dependence bnt does not exhibit true physical (or physiological) dependence. 

Tolerance develops to many of A -THC s effects in heavy marijuana users. Although chronic cannabis use does not result in severe withdrawal symptoms, numerous case reports attest to development of dependence in subjects taking high doses of THC for several weeks. The most prominent symptoms were irritability and restlessness others included insomnia, anorexia, increased sweating, and mild nausea. Cessation of mild or moderate use of marijuana, however, does not produce a withdrawal syndrome. 

A. Amaral. Effect of marijuana in the glucose-tolerance test. Ann N Y Acad Sci 1971 191 54-60. CS037... 

Cross tolerance has been demonstrated between LSD and mescaline, psilocybin, and psilocin. There seems to be no cross tolerance between LSD and marijuana or amphetamine. These observations are indicative of the structural similarites of the compounds. 

Delta-9-tetrahydrocannabinol (THC), the main active ingredient in marijuana, reduces the amount of time spent in REM sleep, although tolerance to this effect can develop over time and the overall amount of time spent in REM sleep returns to normal levels. However, like people who constantly drink alcohol or take narcotic pain relievers, people who smoke marijuana daily can experience REM rebound after stopping the drug. 

Babor, T.F. et al., Marijuana, affect and tolerance a study of subchronic self-administration in women, NIDA Res. Monogn, 49, 199-204, 1984. 

A9-Tetrahydrocannabinol is the major psychoactive cannabinoid in marijuana (Cannabis sativa). Its synthetic form, dronabinol, became available in the U.S. in 1985 as an antiemetic for patients receiving emetogenic chemotherapy. However, it is seldom used as a first-line antiemetic because of its psychoactive effects, and its use is usually limited to patients who have a low tolerance or minimal response to other antiemetic drugs (see Chapter 18). 

Tolerance to the effects of marijuana clearly exist even though chronic users have described a reversed tolerance and claim that smaller doses of the drug are necessary to produce the desired effects. This effect is probably related to the manner of use and the expectations of the user. Chronic, high-dose cannabis users may experience an abstinence or withdrawal syndrome on abrupt discontinuation of use. Signs and symptoms include irritability, restlessness, nervousness, weight loss, insomnia, and rapid eye movement (REM) rebound. Onset of this syndrome is several hours after the last dose, and it lasts 4 to 5 d. Because withdrawal is not life-threatening, treatment involves little more than supportive therapy with short-term, low doses of benzodiazepines. 

Eating or smoking marijuana has been shown to increase heart rate by 20 to 50 percent. This effect can occur within a few minutes to a quarter of an hour and can last for up to three hours. Because of the brain s tolerance to THC, it has been shown that these effects are temporary. However, marijuana users who do not know about or expect these acute health effects may find them unpleasant or even scary, resulting in panic or anxiety reactions. And, those with heart problems or other physical disorders may have disturbing or even harmful effects as a result of cannabis use. 

After the enactment of the CSA there followed a period of uncertainty as the use of illicit drugs increased. Because of conflicts between the philosophy of enforcement and that of treatment or toleration, a presidential National Commission on Marijuana and Drug Abuse (NCMDA) was established in 1972. Its task was to report within a year on marijuana, its highest priority, and within 2 years on drug abuse in general. The committee s first report recommended that possession of small amounts of marijuana should be decriminalized (i.e., a finable offense not subject to incarceration). The final report appeared in March 1973 and reconfirmed its original recommendation. Despite these recommendations, President Nixon remained opposed to decriminalization. 

The election of Jimmy Carter as President in 1976 ensured a continuation of tolerance to drug use, particularly marijuana. In March 1977, the Special Assistant for Health Issues to the President, and high officials from the DEA, the State Department, the National Institute of Drug Abuse (NIDA), NIMH, the Customs Service, and the Justice Department appeared before the House Select Committee on Narcotics Abuse and Control to argue for the decriminalization of marijuana. The President himself repeated a similar theme before Congress later that year. 

One unexplained characteristic—probably having to do with the differences in cannabinols in a leaf—is that when people use different batches of marijuana, they develop less tolerance than if they use the same grass regularly. 

Marijuana has several effects on the cardiovascular system, and can increase resting heart rate and supine blood pressure and cause postural hypotension. It is associated with an increase in myocardial oxygen demand and a decrease in oxygen supply. Peripheral vasodilatation, with increased blood flow, orthostatic hypotension, and tachycardia, can occur with normal recreational doses of cannabis. High doses of THC taken intravenously have often been associated with ventricular extra beats, a shortened PR interval, and reduced T wave amplitude, to which tolerance readily develops and which are reversible on withdrawal. While the other cardiovascular effects tend to decrease in chronic smokers, the degree of tachycardia continues to be exaggerated with exercise, as shown by bicycle ergometry. 

This patient had taken ecstasy 10 times during the year before, the last time about 3 months before the onset of symptoms. Apart from marijuana, he denied using other substances. He was treated with maximal tolerable doses of levodopa and pramipexole, without improvement. The authors reported that they had no explanation for this patient s symptoms, other than the use of ecstasy. They felt that the parkinsonian symptoms most closely resembled MPTP-induced parkinsonism. They further postulated that this could be a delayed neurotoxic effect of ecstasy in the substantia nigra and striatum and could have occurred as a result of neuronal damage by free radicals. 

Patients who use marijuana may have red eyes, a rapid heartbeat, and apathy and memory problems. Many daily users of marijuana develop tolerance for the rapid heartbeat, and they may also develop lung disease and chronic bronchial irritation. 

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