Safety for Use: Acute Side Effects

4 min read

It is now generally accepted that “…except for the harms associated with smoking, the adverse effects of marijuana use are within the range of effects tolerated for other medications” (Institute of Medicine Report of 1999). This opinion is supported by recent clinical research. Besides abuse and dependency, the main side effects of concern are those on the cardiovascular, immune, and hormonal systems, and on cognitive functions.

Research has shown that cannabis produces acute side effects that are within the range of side effects tolerated for other medicinal drugs. Acute side effects relate mainly to psychological effects (cognitive impairment, altered perception) and circulation (decrease of blood pressure). New research adds to the evidence of cannabis’s interaction with other medicinal drugs, effects on cognitive function, and increased risk of heart attack.

In an anonymous survey of 128 patients in Germany, Switzerland, and Austria on the medical use of dronabinol and natural cannabis products, 71% reported no side effects (Schnelle et al. 1999). 26% reported moderate and 3% severe effects. The overall judgment of “no side effects” was also given in some cases where certain side effects (e.g. dry mouth or anxiety) were experienced but apparently regarded as minor by the subjects.

The first U.S. study using marijuana for people with HIV has found that smoking the plant does not disrupt the effect of antiretroviral drugs that keep the virus in check (Ksel et al. 2002). Kosel and colleagues of San Francisco General Hospital were limited to focusing on marijuana’s safety rather than its effectiveness. The 67 people who participated in the study were kept in the hospital during the 21-day study period. Researchers were especially interested in studying people on drug regimes that contain protease inhibitors, because THC is metabolised by the same system in the liver as those drugs. Subjects on stable regimens involving taking Indinavir 800 mg every 8 h (n = 28) or Nelfinavir 750 mg three time a day (n = 34) were randomized to one of three treatment arms: 3.95% THC marijuana cigarettes, dronabinol 2.5 mg capsules, or placebo capsules administered three times daily. Serial blood sampling was performed at baseline and on day 14 of treatment. In all groups the level of virus in the blood dropped or remained undetectable by current tests. There was no statistically significant difference among the three groups, with those taking THC or marijuana having slightly lower levels. With regard to the pharmacokientic data, the authors stated:

“Despite a statistically significant decrease in C(max) of IDV in the marijuana arm, the magnitude of changes in IDV and NFV pharmacokinetic parameters in the marijuana arm are likely to have no short-term clinical consequence. The use of marijuana or dronabinol is unlikely to impact antiretroviral efficacy” (Kosel et al. 2002)

Lead researcher Donald Abrahms concluded:

“Controlled clinical trials investigating smoked marijuana can be safely conducted. Neither smoked nor oral cannabinoids have an adverse effect on HIV RNA levels, immune parameters or protease inhibitor kinetics over a 21 day treatment period in patients with HIV infection on a stable antiretroviral therapy regimen. Use of both smoked marijuana and dronabinol lead to increased weight gain compared to placebo. Further studies to investigate the therapeutic potential of smoked marijuana and other cannabinoids are warranted.” (Abrahms et al, 2002)

Although the ability to perform complex cognitive operations is assumed to be impaired following acute marijuana smoking, complex cognitive performance after acute marijuana use has not been adequately assessed under experimental conditions. In a study by Hart et al. (2001) an inter-participant double-blind design was used to evaluate the effects of acute marijuana smoking on complex cognitive performance in experienced marijuana smokers. Acute marijuana smoking produced only minimal effects on complex cognitive task performance:

“Eighteen healthy research volunteers (8 females, 10 males), averaging 24 marijuana cigarettes per week, completed this three-session outpatient study; sessions were separated by at least 72-hrs. During sessions, participants completed baseline computerized cognitive tasks, smoked a single marijuana cigarette (0%, 1.8%, or 3.9% Delta(9)-THC w/w), and completed additional cognitive tasks. Blood pressure, heart rate, and subjective effects were also assessed throughout sessions. Marijuana cigarettes were administered in a double-blind fashion and the sequence of Delta(9)-THC concentration order was balanced across participants. Although marijuana significantly increased the number of premature responses and the time participants required to complete several tasks, it had no effect on accuracy on measures of cognitive flexibility, mental calculation, and reasoning. Additionally, heart rate and several subjective-effect ratings (e.g., “Good Drug Effect,” “High,” “Mellow”) were significantly increased in a Delta(9)-THC concentration-dependent manner. These data demonstrate that acute marijuana smoking produced minimal effects on complex cognitive task performance in experienced marijuana users” (Hart et al. 2001).

Moderate smoking of cannabis increases the risk of a heart attack for middle-aged and elderly users during the first hour after using the drug, a study published in 2001 says (Mittleman et al. 2001). A small portion (0.2%) of patients suffering from a heart attack had smoked cannabis shortly before symptoms began. Cannabis has an influence on blood pressure and heart rate. This may be of relevance for people with coronary heart disease, as are several other drugs that influence circulation. Of the 3882 patients suffering a heart attack, 124 reported smoking marijuana in the previous year, among them 9 within 1 hour of heart attack symptoms. The risk of heart attack onset was significantly elevated 4.8 times over baseline (95% confidence interval: 2.4-9.5) in the first hour after cannabis use. In the second hour it was 1.7 times greater, and returned to baseline afterwards. Murray Mittleman, a professor at Harvard Medical School and director of cardiovascular epidemiology at Beth Israel-Deaconess Medical Centre, and his colleagues wrote in their publication that smoking marijuana is “a rare trigger of acute myocardial infarction”. He noted that cannabis was about as risky as taking a walk for an active person with heart disease, or as sex for a patient with sedentary life style.

Much research has been conducted to address the question of driving ability under the influence of the drug. For example, a major recent study by the UK Transport Research Laboratory found that one single glass of wine impairs driving ability more than smoking a cannabis cigarette (New Scientist of 19 March 2002). The study also found that drivers on cannabis tended to be aware of their intoxicated state, and drove more cautiously to compensate their impairment. This is in good agreement with earlier research of recent years (reviews: Smiley 1999, Chesher & Longo 2002). Another study investigated the effects of chronic exposure to cannabis on the effects of alcohol on driving-related psychomotor skills. Chronic cannabis use (in the absence of acute administration) did not potentiate the effects of alcohol. In fact, the regular users showed lower scores for dizziness and a superior tracking accuracy compared to infrequent users after they consumed alcohol (Wright & Terry 2002).


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