Hallucinogens are classified by 1) their molecular structure or 2) their direct neurobiological activity (Bakalar and Grinspoon 1997). The two most common structural subgroups are indoles and phenethylamines. Indoles include lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), psilocybin, ibogaine, and harmaline. Phenethylamines include naturally occurring compounds such as mescaline as well as an ever-expanding number of synthetic variations, such as 4-bromo-2,5-dimethoxyphenethylamine (2C-B), 3,4-methylenedioxy-N- methylamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and 2,5-dimethoxy-4-methylamphetamine (DOM).
Classical hallucinogens work by direct agonism of the 5-HT2A serotonin re- ceptor and include psilocybin, LSD, mescaline, and DMT. Although these com- pounds share neurobiological activity, they come from quite diverse sources: psilocybin can be isolated from a mushroom; DMT is found in a South Amer- ican vine and is also endogenously elaborated by the pineal gland; mescaline de- rives from a cactus in the American Southwest; and LSD is an ergot derivative that can be synthesized in a laboratory.
Hallucinogens may also exert their psychoactive effects by serotonin release or nonspecific serotonin receptor activation, as in the case of MDMA (“ecstasy” or “Molly”‘) and some phenethylamines; by N-methyl-D-aspartate (NMDA)
receptor or glutamatergic modulation, such as ketamine, phencyclidine, and other dissociative anesthetics; by cannabinoid receptor activation; and by N receptor agonism, as occurs with Salvia divinorum. These mechanisms are by no means exhaustive; there are other compounds (e.g., nitrous oxide and the fly agaric mushroom) that work by quite different mechanisms. Interestingly, recent research suggests that hallucinogens, despite their apparent differences in neurobiological activity, work by a common final pathway of prefrontal glu- tamatergic modulation (Vollenweider and Kometer 2010).
The psychoactive effects of these different compounds can be markedly dif- ferent (see Boxes 5–1 and 5–2). Even compounds from the same subgroup (e.g., DMT and psilocybin) can be quite dissimilar. It is therefore beyond the purview of this chapter to provide a meticulous examination of the unique effects of each hallucinogen. Instead, we aim to describe all potential hallucinogenic effects. Classical hallucinogens are the subgroup that typically exhibits the widest range of these effects.
Box 5–1. DSM-5 Criteria for Phencyclidine Intoxication
A. Recent use of phencyclidine (or a pharmacologically similar substance). B. Clinically significant problematic behavioral changes (e.g., belliger- ence, assaultiveness, impulsiveness, unpredictability, psychomotor agitation, impaired judgment) that developed during, or shortly after, phencyclidine use.
C. Within 1 hour, two (or more) of the following signs or symptoms: Note: When the drug is smoked, “snorted,” or used intravenously, the on- set may be particularly rapid.
1. Vertical or horizontal nystagmus. 2. Hypertension or tachycardia.
3. Numbness or diminished responsiveness to pain. 4. Ataxia.
5. Dysarthria. 6. Muscle rigidity. 7. Seizures or coma. 8. Hyperacusis.
D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxi- cation with another substance.
Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code de- pends on whether there is a comorbid phencyclidine use disorder. If a mild phencyclidine use disorder is comorbid, the ICD-10-CM code is F16.129, and if a moderate or severe phencyclidine use disorder is comorbid, the ICD-10-CM code is F16.229. If there is no comorbid phencyclidine use dis- order, then the ICD-10-CM code is F16.929.
Source. Reprinted from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Washington, DC, American Psychiatric Association, 2013. Used with permission. Copyright © 2013 American Psychiatric Association.
Hallucinogenic alterations can be grouped into three categories, all of which can be experienced concurrently. Most narratives offered by individuals who have undergone a hallucinogenic experience suggest a progression of effects in which one category of alterations is necessary for the next to emerge. The first and most basic are perceptual changes. These include an intensification of sen- sory phenomena; greater sensitivity to latent phenomena, such as patterns or textures ordinarily overlooked; changes in the perception of time or space; con- flation of sensory modalities, as in synesthesia; the production of eidetic imag- ery, such as spirals, shapes, and arabesques; greater aesthetic appreciation; illusions; pseudo hallucinations (with intact reality testing); and an altered sense of the body.
Box 5–2. DSM-5 Criteria for Other Hallucinogen Intoxication
A. Recent use of a hallucinogen (other than phencyclidine).
B. Clinically significant problematic behavioral or psychological changes (e.g., marked anxiety or depression, ideas of reference, fear of “losing one’s mind,” paranoid ideation, impaired judgment) that developed dur- ing, or shortly after, hallucinogen use.
C. Perceptual changes occurring in a state of full wakefulness and alert- ness (e.g., subjective intensification of perceptions, depersonalization, derealization, illusions, hallucinations, synesthesias) that developed during, or shortly after, hallucinogen use.
D. Two (or more) of the following signs developing during, or shortly after, hallucinogen use: 1. Pupillary dilation. 2. Tachycardia. 3. Sweating. 4. Palpitations. 5. Blurring of vision. 6. Tremors. 7. Incoordination.
E. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intox- ication with another substance.
Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code de-
pends on whether there is a comorbid hallucinogen use disorder. If a mild hallucinogen use disorder is comorbid, the ICD-10-CM code is F16.129, and if a moderate or severe hallucinogen use disorder is comorbid, the ICD- 10-CM code is F16.229. If there is no comorbid hallucinogen use disorder, then the ICD-10-CM code is F16.929.
Source. Reprinted from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Washington, DC, American Psychiatric Association, 2013. Used with permission. Copyright © 2013 American Psychiatric Association.
The second category of alterations is experiential. These changes include alterations in mood (euphoria, hilarity, terror, or anxiety), altered relatedness to others (empathy, alienation, connectedness, or merging), philosophical or exis- tential concerns, increased insight, dissociation, emergence of pseudo delusional or overvalued ideas (e.g., the world will end in the near future), suggestibility, resurgence of past or apparently resolved conflicts, and near-death or birth-like experiences.
Mystical or transpersonal experiences constitute the third category. These are experiences characterized by heightened spirituality or mysticism, similar in nature to those reported by mystics or religious figures throughout history. They can include a struggle or conflict of archetypal dimensions, a sense of life’s
fundamental absurdity, immersion in a total void, a sense of the sacred, spiritual ecstasy, spatiotemporal transcendence, nondiscursive understanding (e.g., knowledge beyond the pale of words or concepts), ego dissolution, an over- whelming sense of finiteness or sinfulness, identification with the divine, rein- carnation, reevaluation of values, redemption, or metaphysical or cosmological speculation. Recent research with psilocybin suggests that the personal signifi- cance of such experiences can be enduring, with individuals continuing to report 1 year later that the experience was among the most important in their lives (Griffiths et al. 2006).
Anecdotal reports suggest that hallucinogenic alterations are shaped, to an extent, by the psychology, past experience, expectations or intentions, and attri- butes of the individual (the set), as well as by the environment (including other individuals or a guide if present) in which the experience occurs (the setting). The set and setting may also play a primary role with regard to whether the hal- lucinogen experience is pleasant and enriching (“a good trip”) or dysphoric and upsetting (“a bad trip”).