Substance Abuse: Hallucinogen- and MDMA-Related Disorders

Substance Abuse: Hallucinogen- and  MDMA-Related Disorders

Hallucinogens alter perception, cognition and mood as their pri-mary psychobiological action in the presence of an otherwise clear sensorium. LSD is the most common hallucinogen and is readily and cheaply available in the USA. Unlike the chronic use of stimu-lants amphetamine and cocaine, chronic use of hallucinogen does not lead to physiological dependence. On the other hand tolerance to LSD builds in 4 to 7 days. There is no withdrawal or documented fatalities from overdose of LSD. The 3,4-methylenedioxymeth-amphetamine (MDMA or Ecstasy) is a synthetic amphetamine analogue that is used to enhance affiliative emotional responses. Its use appears to be increasing, particularly among young adults. Dependence and escalation of dosage are uncommon. All these agents are neurotoxic with deleterious effects on serotonergic neurons, memory and mood. Common naturally occurring com-pounds include mescaline (and peyote), psilocybin and dimethyl-tryptamine (DMT). The dawn of modernity for synthetic halluci-nogenic drugs can be placed tothe moment in 1943 when Albert Hofmann, a Swiss chemist, discovered the potent psychological effects of LSD. The definition of an hallucinogenic drug has been a matter of controversy. To address the problem of classification, one may define as hallucinogenic “any agent which has alterations in perception, cognition, or mood as its primary psychobiological actions in the presence of an otherwise clear sensorium”.

Epidemiology of Hallucinogen Abuse

Among hallucinogens, LSD remains the most popular in its class among American high school students. An annual drug survey of 45 000 students by the Monitoring the Future Program of the Uni-versity of Michigan has been performed since 1975. There is a sta-ble long-term trend of LSD lifetime use among one in 10 seniors.

Etiology and Pathophysiology

The acute effects of “tripping” on LSD-like (i.e, with similar psychic effects, such as psilocybin or mescaline) hallucinogens are variable and profound. Table 40.1 illustrates a typical time course for the psychiatric effects of LSD.

The effective hallucinogenic doses vary widely between drugs in this class, and between individuals. The conventional explanation of this variability of response is instructional set, anticipation of drug effects due to previous experience, and

environmental setting affect outcome. Additionally, personal-ity, preexisting mental illness and genetic vulnerability are also likely to be important. Unlike the chronic use of stimulants like amphetamine and cocaine, chronic use of hallucinogens does not lead to physiological dependence. On the other hand, tolerance to LSD rapidly builds in 4 to 7 days, and lasts 3 days. Titeler and colleagues (1988) have shown that hallucinogenic potency of LSD and selected phenylisopropylamines correlates with the drug’s ability to bind at the postsynaptic 5-HT₂ receptor.

Hallucinogens simultaneously decrease spontaneous ac-tivity in the locus coeruleus, considered a novelty detector in the midbrain, while enhancing sensory responses of the locus coeru-leus by activating N-methyl-D-aspartate receptors. In the cerebral cortex, the drugs both inhibit and induce activity by exciting GABAergic and glutamatergic neurons respectively

The presence of selective serotonin reuptake inhibitors blunts hallucinogenic effects, possibly through the activation of 5-HT₁ receptors (Aghajanian and Marek, 1999). GABA-_A antianx-iety agents (e.g., benzodiazepines) promptly bring a bad trip to an end, presumably by inhibition of the locus coeruleus. Opiates are likely to have a similar outcome by reducing glutamatergic excitation of cortical systems. This may explain why hallucinogen abuse appears to be so uncommon among active opioid abusers.