Physiologic changes accompany and often precede the perceptual changes induced by lysergamides, tryptamines, and phenylethylamines. The physical effects may be caused by direct drug effect or by a response to the disturbing or enjoyable hallucinogenic experience. Sympathetic effects mediated by the locus coeruleus include mydriasis, tachycardia, hypertension, tachypnea, hyperthermia, and diaphoresis. They may occur shortly after ingestion and often precede the hallucinogenic effects. Other clinical findings that are reported include piloerection, dizziness, hyperactivity, muscle weakness, ataxia, altered mental status, coma, and rhythmic, pupillary dilation, and constriction.72 Nausea and vomiting often precede the psychedelic effects produced by psilocybin and mescaline. Potentially life-threatening complications, such as hyperthermia, coma, respiratory arrest, hypertension, tachycardia, and coagulopathy, were described in a report of eight patients with a massive LSD overdose.68 Sympathomimetic effects are generally less prominent in LSD toxicity than in phenylethylamine toxicity. Similar sympathetic symptoms are described after the use of 2C-B and 2C-T-7. Low doses of 2C-B and 2C-T-7 may produce hypertension, tachycardia, and visual hallucinations, while elevated doses are associated with shifts in color perception, enhanced auditory, and visual stimulation. Three deaths are associated with 2C-T-7 use; in one case, death may have resulted from seizures or aspiration.34,39 An analog of 2C-B, called 2C-B-FLY, or Bromo-dragonFLY, is implicated in finger necrosis that requires amputation secondary to potent peripheral vasospastic activity as well as sudden cardiac death.96 Similar vasoconstrictive effects resulting in limb ischemia may be induced by exposure to ergot containing alkaloids.
The psychological effects of hallucinogens seem to represent a complex and elusive interaction between different neurotransmitters, including the serotonergic and dopaminergic systems. Based on this serotonergic mechanism, serotonin toxicity could theoretically occur after the use of any of the lysergamide, indolealkylamine or phenylethylamine hallucinogens. Animal studies have documented LSD and tryptamine-induced serotonin toxicity.117,132 Case reports have linked phenylethylamine use to fatal serotonin toxicity in recreational users.92,133
Tolerance to the psychological effects of LSD occurs within 2 to 3 days with daily dosing, but rapidly dissipates if the drug is withheld for two days. Psychological cross-tolerance among mescaline, psilocybin, and LSD is reported in humans.14 There is no evidence for physiologic tolerance, physiologic dependence, or a withdrawal syndrome with LSD. Limited cross-tolerance is demonstrated between psilocybin and cannabinoids such as marijuana.22
Salvia divinorum use results in vivid hallucinations and synesthesia.116 Additionally, its use may cause diuresis, nausea, and dysphoria. These aversive effects may limit its long-term recurrent use.10
The dual stimulant and sedative properties of Kratom contributed to its traditional use among manual laborers. However, its opioidlike activity has led to a surge in contemporary use as an herbal treatment for opioid withdrawal among patients with chronic pain.18,19 Anorexia, weight loss, and insomnia are reported among Kratom addicts. Hyperpigmentation of the cheeks is also described among chronic users.123
Recreational nutmeg use results in the desired effects of euphoria and hallucinations, as well as the adverse effects of nausea, vomiting, dizziness, flushing, tachycardia, and hypotension. Two case reports of fatalities from nutmeg ingestion are reported; however, it is unclear if these deaths truly represent nutmeg toxicity.29,119
The belladonna alkaloids produce classic signs of anticholinergic toxicity, including hyperthermia, tachycardia, mydriasis, flushing, anhidrosis, urinary retention, and ileus. The central effects can include restlessness, hallucinations, agitation, delirium, seizures, and coma.31 The psychosis produced by belladonna alkaloids can be profound; in one case, a young man autoamputated his tongue and penis after ingestion of tea made from Angel’s trumpet.81
The vast majority of morbidity from hallucinogen use stems from trauma. Hallucinogen users frequently report lacerations and bruises sustained during their “high.” Additionally, dysphoria may drive patients to react to stimuli with unpredictable, and occasionally, aggressive behaviors. Many Internet sites regarding hallucinogen use advise readers to take hallucinogens only while under the supervision of a “sitter.”40
The psychological effects of hallucinogens are dose related and affect changes in arousal, emotion, perception, thought process, and self-image. The response to the drug is related to the person’s mindset, emotions, or expectations at the time of exposure and can be altered by the group or setting.1 The person experiencing the effects of a hallucinogen is usually fully alert, oriented, and aware that he or she is under the influence of a drug. Euphoria, dysphoria, and emotional lability may occur.
Illusions are common, typically involving distortion of body image and alteration in visual perceptions. Hallucinogen users may display acute attention to details with excessive attachment of meaning to ordinary objects and events. Usual thoughts seem novel and profound. Many people report an intensification of their sensory perceptions such as sound magnification and distortion. Colors often seem brighter with halolike lights around objects. Frequently, hallucinogen users relate a sense of depersonalization and separation from the environment, commonly called an “out-of-body” experience. Synesthesias, or sensory misperceptions, such as “hearing colors,” or “seeing sounds” are commonly described. Hallucinations may be visual, auditory, tactile, or olfactory.
Acute adverse psychiatric effects of hallucinogens include panic reactions, psychosis, and major depressive dysphoric reactions. Acute panic reactions, the most common adverse effect, present with frightening illusions, tremendous anxiety, apprehension, and a terrifying sense of loss of self-control.46 These psychiatric effects may cause patients to seek care in the emergency department.