Hallucinogens effects

Some neuroleptics, including clozapine, are potent 5-HT-receptor antagonists and the possible role of 5-HT in the action of neuroleptics and the development of schizophrenia has recently generated much interest (Busatto and Kerwin 1997). This has centred primarily on 5-HT2A receptors found in the limbic cortex, which are linked to neuronal excitation and believed to mediate the hallucinogenic effects of drugs such as lysergic acid diethylamide (LSD). 

Recent controversy about the recreational abuse and potential therapeutic use of designer drugs has focused attention on MDA (methylenedioxyampheta-mine HCl) and structurally related phenylisopropylamine compounds, including MDMA istructural analogs of the psychomotor stimulant amphetamine and the hallucinogen mescaline, and produce stimulant and/or hallucinogenic effects (Shulgin 1978). 

MDMA stimulates the CNS, causes euphoria and relaxation, and produces a mild hallucinogenic effect. It can cause muscle tension, nausea, faintness, chills, sweating, panic, anxiety, depression, hallucinations, and paranoid thinking. It increases heart rate and blood pressure and destroys serotonin (5-HT)-producing neurons in animals. It is considered to be neurotoxic in humans. 

Siegel, R. K., Collings, P. R., and Diaz, J. L. (1977) On the use of Tagetes lucida and Nicotiana rustica as a Huichol smoking mixture The Aztec Yahutli with suggestive hallucinogenic effects. Economic Botany, 31 16-23. 

In summary, primary amine and monoalkyl derivatives of tryptamine have not yet been demonstrated to produce hallucinogenic effects in man or to consistently produce profound behavioral effects in animals. Admittedly, relatively few compounds have been examined, and few studies have been conducted. Nevertheless, present evidence suggests that these derivatives, by virtue of their inability to penetrate the blood-brain barrier and/or their rapid metabolism, may not be able to achieve adequate brain levels to elicit effects. In some cases, these factors may lead to masking of potential central effects by peripheral actions of the compounds or their metabolites. 

Glennon, R. A., Young, R., and Jacyno, J. M. (1983) Indolealkylamine and phenalkylamine hallucinogens Effect of a-methyl and N-methyl substituents on behavioral activity. Biochem. Pharmacol., 32 1267-1273. 

Results of studies on the role of serotonin-in the action of LSD, which were conducted on human subjects, may be more easily interpreted because they directly examined the hallucinogenic effects of LSD. Prior depletion of brain serotonin with reserpine accentuated the effects of LSD (34,71). As described above, prior treatment with a MAOI attenuated the effects of LSD (38,70) and... 

Ibogaine, discovery of, 7 Imagery, hallucinogen-induced, 15-16 Indole hallucinogens, effects of on spinal reflexes, 38-39 on startle reflexes, 43-44 Indolealkylamines... 

An important methodologic point about the majority of these studies is that they use a reduced preparation, in which the spinal cord is neurally isolated from the brain by a complete transection (129). The rationale for using this simplified preparation is that spinal reflex activity can be analyzed in the absence of supraspinal influences. However, transection may introduce other variables (i.e., ischemia, disruption of the blood-brain barrier, loss of tonic neural activity from supraspinal systems), which may result in drug effects on spinal reflexes that are quantitatively or even qualitatively different than those seen in the intact animal. Thus the following review of hallucinogen effects on spinal reflexes is organized into two main categories (a) studies in transected animals, and (b) those in decerebrate or intact preparations. 

These studies illustrate the point that the analysis of hallucinogen effects on spinal reflexes in intact animals may provide important information regarding the role of tonically active functionally depressant descending systems that would otherwise be lacking in the spinally transected preparation. 

A critical question to ask at this juncture is whether any of these behavioral changes in animals is relevant to the hallucinogenic effects of this class of drugs in humans. In other words, which if any of these animal behaviors might closely model human hallucinations To answer this question, one must examine the... 

While mescaline is a simple 2-phenethylamine derivative, the addition of an alpha-methyl group to the side chain yields Structure 8 (TMA). This simple hybrid of the structures of mescaline and amphetamine retains the hallucinogenic effects of mescaline but possesses about twice the potency of the latter (174,200). Addition of the alpha-methyl to other 3,4,5-substituted compounds generally brings about an approximately twofold increase in potency. The addition of an alpha-methyl to 2,4,5-substituted compounds, however, may dramatically increase activity. For example, 2-(2,4,5-trimethoxyphenyl) ethylamine apparently is clinically inactive (195). Addition of an alpha-methyl gives TMA-2 (Table 1), with 20 times the potency of mescaline. However, the addition of an alpha-methyl does not significantly increase in vitro receptor affinity in either 3,4,5-or 2,4,5-series (72,78). Thus it is probable that the alpha-methyl may confer metabolic stability in vivo. It could also be speculated that this protection is more important in the 2,4,5-substituted series than in 3,4,5-substituted compounds. 

Ketamine is rapidly metabolized by the body, so the hallucinogenic effects of ketamine wear off within an hour or so after taking the drug. However, users say they often experience repeated flashbacks, or sudden memories of the visions or feelings experienced while on the drug. These flashbacks can persist for days, weeks, months, or even a year after a particular trip. 

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