Background
Hallucinogens comprise a unique collection of substances that are ingested to induce alterations of consciousness. A variety of substances with differing chemical structures is known to induce hallucinations when ingested in nontoxic doses. Hallucinations are usually visual, auditory, and tactile, in varying combinations, depending on the substance ingested, the setting, and the experiences of the person using them.
Hallucinogenic substances have been used worldwide for centuries to induce altered states for religious and spiritual purposes. Throughout history, abuse of such substances probably was limited because of the moral and religious significance of their uses.
Hallucinogens can be classified and grouped by chemical structure and the compound from which they are derived. Chemically related substances tend to exhibit similar effects. Many other agents can be classified as pseudohallucinogens because they produce psychotic and delirious effects without the classic visual disturbances of true hallucinogens.
One system groups hallucinogens into 4 major classes that include indole alkaloids, piperidines, phenylethylamines, and cannabinoids. The following is a partial list of the hallucinogens by chemical derivation:
Indole alkaloids
- Lysergic acid diethylamide (LSD)
- Lysergic acid amide (LSA)
Piperidines
- Atropine and scopolamine
- Cocaine
- Phencyclidine (PCP)
- Ketamine
Phenylethylamines
- Mescaline
- 3,4-methylene dioxymethamphetamine (MDMA)
- Methylene dioxyamphetamine (MDA)
- 3-methoxy-4,5-methylene dioxyamphetamine (MMDA)
- 3,5-dimethoxy-4-methylamphetamine (STP)
- 2,5-dimethoxy-4-methylamphetamine (DOM)
Cannabinoids
- Delta-9-tetrahydrocannabinol (THC, the active substance in marijuana)
A number of naturally occurring hallucinogens can be found in plants and mushrooms and grow in many locations in the United States. Many of these substances have been involved in ritualistic medicine for a long time, and some are emerging agents of abuse. Included in these naturally occurring substances are dimethoxytryptamine (DMT), psilocybin and psilocin, mescaline, salvinorin A, LSA, and atropine and scopolamine.
LSD and LSA
LSD first appeared in the United States in 1949. Because of its potent psychotomimetic effects, it was believed to be useful in producing model psychosis for evaluation. As an experimental drug in the 1950s, LSD was used by psychiatrists and psychologists for the treatment of alcoholism and many neuroses.
LSD use also was believed to enhance creativity and promote well-being. By the late 1950s, use of LSD had been proposed as a way to achieve intellectual and spiritual awakening and enlightenment. Initial studies in the early 1960s concluded that the drug was safe. By the mid 1960s, reports of increasing illicit abuse and adverse effects in patients treated with LSD led the federal government to begin regulation and restriction of its use.
Although overall hallucinogen use remains fairly constant, LSD use and street sales of many substances marketed as LSD have increased. Since LSD first appeared on the street, its use and popularity have risen and fallen cyclically.
LSA is a naturally occurring hallucinogen that is a close analog to LSD. LSA is found in a variety of plants, most notably Ipomoea violacea (morning glory), Argyreia nervosa, and Stipa robusta.
Phencyclidine and ketamine
PCP and ketamine are piperidine derivatives with potent anesthetic properties and illusionogenic properties. PCP was initially marketed as an anesthetic but was withdrawn from use because of widespread reports of postanesthetic dysphoria, delirium, and psychotic behavior.
PCP was introduced as a veterinary anesthetic in the late 1960s and, beginning in California, soon became a major drug of abuse. The "peace pill," as it was dubbed in San Francisco, began to be distributed as everything from THC to LSD and often was added to marijuana cigarettes. It commonly is referred to as "angel dust."
Ketamine, a widely used anesthetic, increasingly has been found on the streets and often is ingested by large numbers of people at so-called raves.
Psilocin and psilocybin
These indole alkaloids are found worldwide in a variety of mushrooms and have been used by indigenous peoples of Central America for centuries in religious rites. Ingesting only a few mushrooms may produce hallucinogenic affect, but, generally, large numbers of mushrooms are required. Analysis of street samples of "psilocybin" found that less than one third of the samples actually contained the alkaloid.
Mescaline
Mescaline is a phenylethylamine-derived alkaloid that is found worldwide in a variety of cacti, the best known being the North American peyote cactus. Similar to the mushroom-derived hallucinogens, mescaline in the form of peyote cactus buttons has been used in rituals by many Native Americans for centuries. To achieve the desired effect, 5-10 buttons are chewed and ingested.
Salvinorin A
Salvinorin A is a naturally occurring hallucinogen that is found in a variety of plants but is named from Salvia divinorum, or diviners sage, a member of the mint family.[1] Salvinorin A is unique, in that unlike other known hallucinogenic substances that interact with serotonin (5-HT2 receptors) metabolism, this substance has been identified as the first known naturally occurring kappa-opioid receptor agonist. This substance has been used by the Mazatec Indians in Mexico for ceremonial purposes. Although salvia remains uncontrolled, there are several states that have significantly restricted it, and the Drug Enforcement Agency (DEA) is looking into placing it as a Schedule I controlled substance.[2]
Atropine and scopolamine
Atropine and scopolamine are found in a variety of plants, and overdoses can induce hallucinations as well as a variety of more serious effects. Both are found in Datura stamonium (Jimson weed), Atropa belladonna (Deadly nightshade), and Mandragora officinarum (Mandrake), and scopolamine alone in Hyoscyamus niger (Henbane).
Designer drugs
Designer drugs were originally described as such as they were derived from chemically altered legitimate parent compounds. These drugs were initially derived to circumvent prosecution by the Drug Enforcement Agency. However, changes to federal drug laws in 1986 made all such chemically altered compounds illegal. Most of these substances are chemically derived from methamphetamine, but increasing numbers of opioid-derived substances as well as new classes of agents are appearing in this category. The best known of the hallucinogenic amphetamine derivatives is MDMA, commonly known as "ecstasy."
The following is a list of common designer drugs with hallucinogenic properties and the substances they are derived from:
Amphetamine derivatives
- MDMA (ecstasy)
- MDA[3]
- Methylenedioxyethylamphetamine (MDEA)
- R,S -1-(1',3'-benxodioxol-5'-yl)-2-butanamine (BDB)
- R,S-N -methylbenzodioxolylbutanamine (MBDB)
Piperazine derivatives
- Benzylpiperazines - Benzylpiperazine (BZP), 1-(3,4-methylenedioxybenzyl)piperazine (MDBP)
- Phenylpiperazines -m -Chlorophenylpiperazine (mCPP), trifluoromethylphenylpiperazine (TFMPP), p -methoxyphenylpiperazine (MeOPP)
Pyrrolidinophenone derivatives
- R,S -alpha-pyrrolidinopropiophenone (PPP)
- R,S -4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP)
- R,S -3',4'-methylenedioxy-alpha-pyrrolidinopropiophenone (MDPPP)
- R,S -4'-methyl-alpha-pyrrolidinopropiophenone (MPPP)
- R,S -4'-methyl-alpha-pyrrolidinohexanophenone (MPHP)
Many of the newer designer drugs are also described as belonging to the hallucinogenic tryptamines, of which the naturally occurring agents psilocin, psilocybin, and dimethyltryptamine (DMT) belong. Two of the newest agents in the group are "foxy" (5-MeO-DIPT) and alpha-methyltryptamine (AMT). Other agents in this group include bufotenine, alpha-ethyltryptamine, diethyltryptamine (DET), and 5-MeO-DMT.
Pathophysiology
The major effects are centered in the CNS, although many of these substances produce additional systemic effects similar to those of the compounds from which they originate.[4]
Indole amine derivatives appear to create hallucinogenic effects by acting at the 5-HT2 serotonin receptors. Most indole derivatives also produce sympathomimetic effects. Piperidine derivatives appear to block the reuptake of serotonin, dopamine, and norepinephrine and may block postsynaptic acetylcholine binding. Phenylethylamine derivatives enhance presynaptic release and block reuptake of serotonin and norepinephrine. MDMA (ecstasy) causes a very rapid and powerful release of presynaptic serotonin, and this appears to be related to the damage done to serotonin releasing neurons and the long-term effects on the brain.[5] The cannabinoids' mechanisms of action may involve alteration of the balance of catecholamine and serotonin actions.
Epidemiology
Frequency
United States
The National Institute on Drug Abuse (NIDA) data from 1994 indicate a slight decline in hallucinogen abuse from 1976-1992 but then increased use in 1993 and 1994. In 1994, 2.7% of adolescents aged 12-17 years and 5.1% of adults aged 18-25 years reported using hallucinogens. The Monitoring the Future Study reports an annual rate of LSD use in 8.4% of high school seniors in 1995. Drug Abuse Warning Network (DAWN) reported an increase in LSD-related ED visits in 1994 data. Lifetime hallucinogen use was reported in 8.7% of total respondents to the 1994 National Household Survey on Drug Abuse.
The NIDA "Monitoring the Future"[6] survey results published in October 2008 indicated that, among respondents aged 19-45 years, up to 31% reported at least some use of a hallucinogen in their lifetime. Use in the last year and use in the last month gradually declined with age from 19 years, with no reported use in the last month in respondents older than 35 years.
Race
The latest NIDA data reveal that African Americans in the 12th grade consistently report lower use of most licit and illicit drugs than whites, and the difference is quite large for hallucinogens.[6] This also remains true in the younger age groups. Hispanic 12th graders report the highest use of the most dangerous drugs, namely heroin, cocaine, and methamphetamine.
Sex
NIDA data from 2008 indicate significantly higher use of all hallucinogens in males, with more than a 2-fold use over females.[6] MDMA (ecstasy) use was only moderately higher in males (2.7%) versus females (2%), whereas LSD use was 2.6% in males compared with 0.6% in females.
Age
The overall use of hallucinogens rapidly declines from adolescence through adulthood, and age related prevalence is noted above.[6] Adolescent use of MDMA appears to be a significant risk for exhibiting hallucinogen dependency, as well as other substance abuse disorders.[5]
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