Psychotomimetics Psychedelics Hallucinogens

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Psychotomimetics are able to elicit psychic changes like those manifested in the course of a psychosis, such as illu-sionary distortion of perception and hallucinations. This experience may be of dreamlike character; its emotional or intellectual transposition appears inadequate to the outsider.

A psychotomimetic effect is pictori-ally recorded in the series of portraits drawn by an artist under the influence of lysergic acid diethylamide (LSD). As the intoxicated state waxes and wanes like waves, he reports seeing the face of the portrayed subject turn into a grimace, phosphoresce bluish-purple, and fluctuate in size as if viewed through a moving zoom lens, creating the illusion of abstruse changes in proportion and grotesque motion sequences. The diabolic caricature is perceived as threatening.

Illusions also affect the senses of hearing and smell; sounds (tones) are "experienced" as floating beams and visual impressions as odors ("synesthesia"). Intoxicated individuals see themselves temporarily from the outside and pass judgement on themselves and their condition. The boundary between self and the environment becomes blurred. An elating sense of being one with the other and the cosmos sets in. The sense of time is suspended; there is neither present nor past. Objects are seen that do not exist, and experiences felt that transcend explanation, hence the term "psychedelic" (Greek delosis = revelation) implying expansion of consciousness.

The contents of such illusions and hallucinations can occasionally become extremely threatening ("bad" or "bum trip"); the individual may feel provoked to turn violent or to commit suicide. Intoxication is followed by a phase of intense fatigue, feelings of shame, and humiliating emptiness.

The mechanism of the psychoto-genic effect remains unclear. Some hal lucinogens such as LSD, psilocin, psilocy-bin (from fungi), bufotenin (the cutaneous gland secretion of a toad), mescaline (from the Mexican cactuses Lophophora williamsii and L. diffusa; peyote) bear a structural resemblance to 5-HT (p. 116), and chemically synthesized amphetamine-derived hallucinogens (4-methyl-2,5-dimethoxyamphetamine; 3,4-di-methoxyamphetamine; 2,5-dimethoxy-4-ethyl amphetamine) are thought to interact with the agonist recognition site of the 5-HT2A receptor. Conversely, most of the psychotomimetic effects are annulled by neuroleptics having 5-HT2A antagonist activity (e.g. clozapine, risperidone). The structures of other agents such as tetrahydrocannabinol (from the hemp plant, Cannabis sativa— hashish, marihuana), muscimol (from the fly agaric, Amanita muscaria), or phencyclidine (formerly used as an injectable general anesthetic) do not reveal a similar connection. Hallucinations may also occur as adverse effects after intake of other substances, e.g., scopolamine and other centrally active parasympatholytics.

The popular psychostimulant, me-thylenedioxy-methamphetamine (MDMA, "ecstasy") acutely increases neuronal dopamine and norepinephrine release and causes a delayed and selective degeneration of forebrain 5-HT nerve terminals.

Although development of psychological dependence and permanent psychic damage cannot be considered established sequelae of chronic use of psy-chotomimetics, the manufacture and commercial distribution of these drugs are prohibited (Schedule I, Controlled Drugs).

How Hallucinogens Affect The Brain

Hypothalamic and Hypophyseal Hormones

The endocrine system is controlled by the brain. Nerve cells of the hypothalamus synthesize and release messenger substances that regulate adenohy-pophyseal (AH) hormone release or are themselves secreted into the body as hormones. The latter comprise the so-called neurohypophyseal (NH) hormones.

The axonal processes of hypothalamic neurons project to the neurohypophysis, where they store the nona-peptides vasopressin (= antidiuretic hormone, ADH) and oxytocin and release them on demand into the blood. Thera-peutically (ADH, p. 64, oxytocin, p. 126), these peptide hormones are given pa-renterally or via the nasal mucosa.

The hypothalamic releasing hormones are peptides. They reach their target cells in the AH lobe by way of a portal vascular route consisting of two serially connected capillary beds. The first of these lies in the hypophyseal stalk, the second corresponds to the capillary bed of the AH lobe. Here, the hypothalamic hormones diffuse from the blood to their target cells, whose activity they control. Hormones released from the AH cells enter the blood, in which they are distributed to peripheral organs (1).

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