Lysergic acid provides the nucleus of the ergot alkaloids and it was during a study of derivatives of this in a search for an analeptic that in 1943 a Swiss worker investigating LSD (which structurally resembles nikethamide) felt peculiar and had visual hallucinations. This led him to take a dose of the substance and so to discover its remarkable potency, an effective oral dose being about 30 microgams. The \}/2 is 3 h. (See description of experience, above.) Mechanisms of action are complex and include agonist effect at presynaptic 5-HT receptors in the CNS.
Tachyphylaxis (acute tolerance) occurs to LSD. Psychological dependence may occur; physical dependence does not.
Serious adverse effects include psychotic reactions (which can be delayed in onset) with suicide.
LSD has curious effects in animals: green sunfish become aggressive, Siamese fighting fish float nose up, tail down and goats walk in unaccustomed stereotyped patterns. The elephant exhibits episod
37 Huxley A1964 The doors of preception. Chatto and Windus, London.
ically a form of sexual or delinquent behaviour known as 'musth'.
Mescaline is an alkaloid from the Mexican peyote cactus (derived from the Indian word peyotl, meaning 'divine messenger'), the top of which is cut off and dried and used as 'mescal buttons' in religious ceremonies. Mescaline does not induce serious dependence and the drug has little importance except to members of some North and Central American societies and to psychiatrists and biochemists who are interested in the mechanism of induced psychotic states.
Tenamfetamine ('ecstasy', MDMA: methylenedioxy-methamphetamine) is structurally related to mescaline as well as to amphetamine. It was originally patented in 1914 as an appetite suppressant and has recently achieved widespread popularity as a dance drug at 'rave' parties (where it is deemed necessary to keep pace with the beat and duration of the music; popular names reflect the appearance of the tablets and capsules and include White Dove, White Burger, Red and Black, Denis the Menace). Tenamfetamine stimulates central and peripheral a-and p-adrenoceptors; thus the pharmacological effects are compounded by those of physical exertion, dehydration and heat. In susceptible individuals (poor metabolisers who exhibit the CYP450 2D6 polymorphism) a severe and fatal idiosyncratic reaction may occur with fulminant hyperthermia, convulsions, disseminated intravascular coagulation, rhabdomyolysis, and acute renal and hepatic failure. Treatment includes: activated charcoal, diazepam for convulsions, P-blockade (atenolol) for tachycardia, ablockade (phentolamine) for hypertension, and dantrolene if the rectal temperature exceeds 39°C.
In chronic users, positive emission tomographic (PET) brain scans show selective dysfunction of serotonergic neurones, raising concerns that neurodegenerative changes accompany long-term use of MDMA.
Phencyclidine ('angel dust') was made in a search for a better intravenous anaesthetic. It is structurally related to pethidine. Phencyclidine was found to induce analgesia without unconsciousness, but with amnesia, in man (dissociative anaesthesia). The postoperative course, however, was complicated by psychiatric disturbance. As the interest of anaesthetists waned, so that of psychiatrists grew and the drug has been used in experimental therapy. Ketamine originated from this work. Overdose can cause agitation, abreactions, hallucinations and psychosis, and if severe can result in seizures, coma, hyperthermia, muscular rigidity, and rhabdomyolysis.
Psilocybin is derived from varieties of the fungus Psilocybe ('magic mushrooms') that grow in many countries. It is related to LSD.
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