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Fischer R, Goldman H. 
“Therapeutic Usefulness of Hallucinogenic Drugs as a Function of their Chemical Structure.”. 
Pharmakopsychiat. 1975;8(4):176- 78.
The structure-activity relationships of some hallucinogenic drugs are described. LSD (i) and cyclazocine (3) share the phenylethylamine - pattern (2) 'which is also displayed by mescaline (4). and 'some methoxy substituted amphetamines. The cross-tolerance between LSD and mescaline can be related to this common.structural. element. 'Tolerance to the: hallucinogenic effects of cyclazocine. develop in the same manner as the tolerance to LSD or mescaline and therefore it can be assumed that cross.-tolerance may be induced between LSD and cyclazocine because of the common phenylethylamine configuration. In studies with rats . it was found that i.m. naloxone (0.12 mg/kg) which can block the LSD-like side effects of cyclazocine, also reversed the catalepsy induced by 375 m'g/kg LSD given i.p. The other distinctive structural feature of LSD is the tryptamine structure (see 5), which is--also a structure of psilocybine (6). Therefore cross - tolerance between'LSD, .psilocybin and.tryptamine is expected, but not between mescaline.and psilocybine. LSD binding is primarily.subcortical,. although its effects on regional perfusion of'the brain, and presumably its function is primarily cortical. Studies with psilocybin and delta-9-THC show that these drugs induce a pattern of cerebral perfusion and function that is confined to subcortical regions. It is postulated that drugs with the phenylethylamine structure affect cortical structures while those with the tryptamine structure affect subcortical structures and drugs which contain.both structures such as LSD affect both regions. Studies with hallucinogenic drugs in healthy volunteers show that psilocybin produced practically . no Bad trips'. compared to mescaline and LSD. The possibility of future use of drugs which affect subcortical structures (e.g. psilocybine) in psychotherapy is discussed.
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