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Hallucinogens

Hallucinogenic compounds found in some plants and mushrooms (or their extracts) have been used—mostly during religious rituals—for centuries. Almost all hallucinogens contain nitrogen and are classified as alkaloids. Many hallucinogens have chemical structures similar to those of natural neurotransmitters (e.g., acetylcholine-, serotonin-, or catecholamine-like). While the exact mechanisms by which hallucinogens exert their effects remain unclear, research suggests that these drugs work, at least partially, by temporarily interfering with neurotransmitter action or by binding to their receptor sites. The four most common types of hallucinogens are:

• LSD (d-lysergic acid diethylamide) is one of the most potent mood-changing chemicals. It was discovered in 1938 and is manufactured from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains.
• Peyote is a small, spineless cactus in which the principal active ingredient is mescaline. This plant has been used by natives in northern Mexico and the southwestern United States as a part of religious ceremonies. Mescaline can also be produced through chemical synthesis.
• Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is obtained from certain types of mushrooms that are indigenous to tropical and subtropical regions of South America, Mexico, and the United States. These mushrooms typically contain less than 0.5‰psilocybin plus trace amounts of psilocin, another hallucinogenic substance.
• PCP (phencyclidine) was developed in the 1950s as an intravenous anesthetic. Its use has since been discontinued due to serious adverse effects.

How are hallucinogens abused?

The very same characteristics that led to the incorporation of hallucinogens into ritualistic or spiritual traditions have also led to their propagation as drugs of abuse. Importantly, and unlike most other drugs, the effects of hallucinogens are highly variable and unreliable, producing different effects in different people at different times. This is mainly due to the significant variations in amount and composition of active compounds, particularly in the hallucinogens derived from plants and mushrooms. Because of their unpredictable nature, the use of hallucinogens can be particularly dangerous.

• LSD—Usually taken orally, LSD is sold in tablets, capsules, and, occasionally, liquid form. LSD is often added to absorbent paper, which is then divided into decorated pieces, each equivalent to one dose. The experiences, often referred to as “trips,” are long; typically, they end after about 12 hours.
• Peyote—The top of the peyote cactus, also referred to as the crown, consists of disc-shaped buttons that are cut from the roots and dried. These buttons are generally chewed or soaked in water to produce an intoxicating liquid. The hallucinogenic dose of mescaline is about 0.3 to 0.5 grams, and its effects last about 12 hours. Because the extract is so bitter, some individuals prefer to prepare a tea by boiling the cacti for several hours.
• Psilocybin—Mushrooms containing psilocybin are available fresh or dried and are typically taken orally. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and its biologically active form, psilocin (4-hydroxy-N,N-dimethyltryptamine), cannot be inactivated by cooking or freezing preparations. Thus, they may also be brewed as a tea or added to other foods to mask their bitter flavor. The effects of psilocybin, which appear within 20 minutes of ingestion, last approximately 6 hours.
• PCP—Readily soluble in water or alcohol, PCP is a white crystalline powder that has a distinctive bitter chemical taste. PCP can be mixed easily with dyes and is often sold on the illicit drug market in a variety of tablet, capsule, and colored powder forms that are normally snorted, smoked, or orally ingested. For smoking, PCP is often applied to a leafy material such as mint, parsley, oregano, or marijuana. Depending upon how much and by what route PCP is taken, its effects can last approximately 4-6 hours.

How do hallucinogens affect the brain?

LSD, peyote, psilocybin, and PCP are drugs that cause hallucinations, which are profound distortions in a person's perception of reality. Under the influence of hallucinogens, people see images, hear sounds, and feel sensations that seem real but are not.

Some hallucinogens also produce rapid, intense emotional swings. LSD, peyote, and psilocybin cause their effects by initially disrupting the interaction of nerve cells and the neurotransmitter serotonin. Distributed throughout the brain and spinal cord, the serotonin system is involved in the control of behavioral, perceptual, and regulatory systems, including mood, hunger, body temperature, sexual behavior, muscle control, and sensory perception.

On the other hand, PCP acts mainly through a type of glutamate receptor in the brain that is important for the perception of pain, responses to the environment, and learning and memory.

There have been no properly controlled research studies on the specific effects of these drugs on the human brain, but smaller studies and several case reports have been published documenting some of the effects associated with the use of hallucinogens.

What other adverse effects do hallucinogens have on health?

Unpleasant adverse effects as a result of the use of hallucinogens are not uncommon. These may be due to the large number of psychoactive ingredients in any single source of hallucinogen.

• LSD—The effects of LSD depend largely on the amount taken. LSD causes dilated pupils; can raise body temperature and increase heart rate and blood pressure; and can cause profuse sweating, loss of appetite, sleeplessness, dry mouth, and tremors.
• Peyote—Its effects can be similar to those of LSD, including increased body temperature and heart rate, uncoordinated movements (ataxia), profound sweating, and flushing. The active ingredient mescaline has also been associated, in at least one report, to fetal abnormalities.
• Psilocybin—It can produce muscle relaxation or weakness, ataxia, excessive pupil dilation, nausea, vomiting, and drowsiness. Individuals who abuse psilocybin mushrooms also risk poisoning if one of many existing varieties of poisonous mushrooms is incorrectly identified as a psilocybin mushroom.
• PCP—At low-to-moderate doses, physiological effects of PCP include a slight increase in breathing rate and a pronounced rise in blood pressure and pulse rate. Breathing becomes shallow; flushing and profuse sweating, generalized numbness of the extremities, and loss of muscular coordination may occur.
  At high doses, blood pressure, pulse rate, and respiration drop. This may be accompanied by nausea, vomiting, blurred vision, flicking up and down of the eyes, drooling, loss of balance, and dizziness. PCP abusers are often brought to emergency rooms because of overdose or because of the drug's severe untoward psychological effects. While intoxicated, PCP abusers may become violent or suicidal and are therefore dangerous to themselves and others. High doses of PCP can also cause seizures, coma, and death (though death more often results from accidental injury or suicide during PCP intoxication). Because PCP can also have sedative effects, interactions with other central nervous system depressants, such as alcohol and benzodiazepines, can also lead to coma.

What treatment options exist?

Treatment for alkaloid hallucinogen (such as psilocybin) intoxication—which is mostly symptomatic—is often sought as a result of bad trips, during which a patient may, for example, hurt him- or herself. Treatment is usually supportive: provision of a quiet room with little sensory stimulation. Occasionally, benzodiazepines are used to control extreme agitation or seizures.

There is very little published data on treatment outcomes for PCP intoxication. Doctors should consider that acute adverse reactions may be the result of drug synergy with alcohol. Current research efforts to manage a life-threatening PCP overdose are focused on a passive immunization approach through the development of anti-PCP antibodies. There are no specific treatments for PCP abuse and addiction, but inpatient and/or behavioral treatments can be helpful for patients with a variety of addictions, including that to PCP.

How widespread is the abuse of hallucinogens?

According to the National Survey on Drug Use and Health (NSDUH), there were approximately 1.1 million persons aged 12 or older in 2007 who reported using hallucinogens for the first time within the past 12 months.

Resources

1. Fantegrossi, W.E., Murnane, K.S., and Reissig, C.J. (2008). The behavioral pharmacology of hallucinogens. Biochem Pharmacol, 75(1), 17-33.
2. Cunningham N. (2008). Hallucinogenic plants of abuse. Emerg Med Australas, 20(2), 167-174.
3. Gilmore HT. (2001). Peyote use during pregnancy. S D J Med, 54(1), 27-29.
4. Attema-de Jonge, M.E., Portier, C.B., and Franssen, E.J. (2007). Automutilation after consumption of hallucinogenic mushrooms. Ned Tijdschr Geneeskd, 151(52) 2869-2872.
5. Schwartz, R.H. and Smith, D.E. (1988). Clin Pediatr (Phila), 27(2) 70-73.
6. Kosten, T. and Owens, S.M. (2005). Immunotherapy for the treatment of drug abuse. Pharmacol Ther, 108(1) 76-85.