Marijuana is the most commonly used illicit drug in the United States. The effects, when taken by inhaling the smoke from cigarettes or pipe, are prompt in onset and evanescent. With low doses, the symptoms are like those of mild alcohol intoxication (drowsiness, euphoria, and perceptual distortions). With increasing amounts, the effects may become similar to hallucinogens (see later); they may be quite disabling for many hours. With even larger doses, severe depression and stupor may occur, but death is rare (for a full account, see Hollister [1988]). No damage to the nervous system has been found after chronic use.
As summarized by Iverson, this agent activates the CB1 receptor, mainly on GABA-ergic neurons in the hippocampus, amygdala, and cortex. Activation of the receptor inhibits the release of oligopeptide neurotransmitters and monoamines. They also have complex electrophysiologic effects on neurons.
Reverse tolerance to marijuana (i.e., increasing sensitization) may be observed initially, but on continued use, tolerance to the euphoriant effects develops. In one of the few experimental studies of chronic marijuana use, the subjects reported feeling “jittery” during the first 24 h after abrupt cessation of smoking marijuana, although no objective withdrawal signs could be detected. Chronic intoxicated users demonstrate reduced cognitive performance, but according to Iverson, a persistent cognitive decline has not been shown definitely.
The mild antiemetic effects of marijuana coupled with euphoria have led to its therapeutic use to ameliorate the effects of chemotherapy. Putative effects on spasticity and, more popularly on neuropathic pain have not been fully substantiated (see commentaries by Caulley, Caplan and Ross).
With the cathionines discussed above, this is a newer class of synthetic drugs; they go by street names of “Spice,” “K2,” “K4,” and many others. These agents bind even more avidly to cannabinoid receptors than does the original drug (marijuana) and produce a heightened stimulant effect. Agitation, delusions, and paranoia result, a veritable psychosis, and some patients we have admitted have been physically almost uncontrollable, only to awaken and have entirely normal affect and cognition. Because the synthetic agents are chemically quite different from cannabis, they do not appear on conventional toxicology-drug screens. Small regional outbreaks of “zombie” like have been attributed to these agents and the difficulty in rapidly identifying the agent has been highlighted by Adams and colleagues. Treatment of intoxication is generally by diazepines and haloperidol but often to little avail until the drug is metabolized.
Mescaline, LSD, and Psilocybin
These drugs produce much the same clinical effects if given in comparable amounts. The perceptual changes are the most dramatic: the user describes vivid visual hallucinations, alterations in the shape and color of objects, unusual dreams, and feelings of depersonalization. An increase in auditory acuity has been described but auditory hallucinations are rare. Cognitive functions are difficult to assess because of inattention, drowsiness, and inability to cooperate in mental testing. The somatic symptoms consist of dizziness, nausea, paresthesia, and blurring of vision. Sympathomimetic effects—pupillary dilatation, piloerection, hyperthermia, and tachycardia—are prominent, and the user may also show hyperreflexia, incoordination of the limbs, and ataxia.
Tolerance to LSD, mescaline, and psilocybin develops rapidly, even on a once-daily dosage. Furthermore, subjects tolerant to any one of these three drugs are cross-tolerant to the other two. Tolerance is lost rapidly when the drugs are discontinued and no characteristic signs of physical dependence ensue. In this sense, addiction does not develop, although users may become psychologically dependent upon the drugs.