Harris Isbell

Cross tolerance between LSD and psilocybin.

Summary1.In two experiments, using a cross-over design, the development of “direct” tolerance to LSD and psilocybin was measured after 10 (Experiment I) or 9 (Experiment II) volunteers had taken LSD in doses increasing to 1.5 meg/kg over the course of 6–7 days (Experiment I) or 13 days (Experiment II). On another occasion, the same patients received psilocybin in doses increasing to 150 mcg/kg over the course of 6–7 days (Experiment I) or 210 mcg/kg over the course of 13 days (Experiment II).2.The development of “cross” tolerance to psilocybin in patients “directly” tolerant to LSD was measured by “challenging” the patients, after they had received LSD chronically, with 150 mcg/kg (Experiment I) or 210 mcg/kg (Experiment II) of psilocybin. “Cross” tolerance to LSD was evaluated by “challenging” the patients, after they had received psilocybin chronically, with 1.5 meg/kg of LSD.3.A high degree of “direct” tolerance to LSD developed in both experiments, as manifested by statistically significant reductions in six of the seven parameters of response. Patients “directly” tolerant to LSD were also “cross” tolerant to psilocybin on five (Experiment I) or four (Experiment II) parameters.4.Definite “direct” tolerance also developed after chronic administration of psilocybin in both experiments, but statistically significant reductions occurred in fewer parameters of response (four in Experiment I and three in Experiment II) than was the case with LSD. Patients chronically treated with psilocybin were also “cross” tolerant to LSD on four (Experiment I) or three (Experiment II) measurements. The degree of “direct” tolerance to psilocybin was less than the degree of “direct” tolerance to LSD.5.The development of “cross” tolerance between LSD and psilocybin reinforces the idea that these two drugs cause psychic disturbances by acting on some common mechanism, or on mechanisms acting through a common final pathway.

Comparison of the reactions induced by psilocybin and LSD-25 in man

Summary1.The reaction induced by oral administration of 57 to 114 mcgm/kg of 0-Phosphoryl-4-hydroxy-N-dimethyltryptamine (psilocybin) has been compared with that induced by a placebo and LSD-25 (1.0 to 1.5 mcgm/kg) in 9 subjects.2.Both LSD and psilocybin caused elevations in body temperature, pulse and respiratory rates, and systolic blood pressure. Threshold for elicitation of the kneejerk was decreased by both drugs.3.After both drugs, abnormal mental states characterized by feelings of strangeness, difficulty in thinking, anxiety, altered sensory perception (particularly visual), elementary and true visual hallucinations, and alterations of body image were reported by the subjects.4.The effects of psilocybin did not persist as long as those of LSD.5.LSD is 100 to 150 times as potent as psilocybin.

Cross tolerance between mescaline and LSD-25, with a comparison of the mescaline and LSD reactions.

Summary1.The reactions caused by intramuscular administration of 0.75 mcg/ kg and 1.5 meg/kg of LSD-25 have been compared in the same 10 subjects with those induced by 2.5 mg/kg and 5.0 mg/kg of mescaline.2.Both LSD and mescaline caused dilatation of the pupils, increase in body temperature, elevation of pulse rate and increase in systolic blood pressure. Both drugs decreased the threshold for elicitation of the kneejerk.3.After both drugs, similar abnormal mental states characterized by anxiety, difficulty in thinking, alteration in mood (generally euphoric), altered sensory perception (particularly visual), elementary and true visual hallucinations and alterations of body image were reported by the subjects.4.The effects of mescaline appeared more slowly and persisted somewhat longer than did the effects of LSD.5.LSD tartrate is 2400–4900 times as potent as mescaline hydrochloride. On a molecular basis, LSD is 4500 to 9275 times as potent as mescaline.6.Patients receiving LSD daily developed direct tolerance to LSD; such patients were also cross tolerant to mescaline. Likewise patients receiving mescaline daily became tolerant to mescaline and cross tolerant to LSD.7.It was inferred that LSD, psilocybin and mescaline probably share common mechanisms of action or some common final pathway.

Relationships of psychotomimetic to anti-serotonin potencies of congeners of lysergic acid diethylamide (LSD-25).

Summary1.The psychotomimetic potency of 13 congeners of LSD-25 has been approximately determined in man.2.With the exception of acetylation of the indole nitrogen, all the changes made in the LSD molecule reduced psychotomimetic potency. Bromination at carbon 2 caused the greatest inactivation.3.High potency as a serotonin antagonist in isolated smooth muscle preparations was not correlated with high potency as a psychotomimetic.4.The data do not support but do not disprove the “serotonin deficiency” hypothesis of the LSD psychosis.

Cross tolerance between D-2-brom-lysergic acid diethylamide (BOL-148) and the D-diethylamide of lysergic acid (LSD-25).

Summary1.Simultaneous administration of 2 to 4 mg of d-2-Brom lysergic acid diethylamide (BOL-148) did not reduce the intensity of the reaction caused by 0.5 to 1.5mcg/kg of LSD-25.2.Pre-treatment of 8 subjects with 3 mg of BOL-148 daily for two days caused statistically nonsignificant reductions in all aspects of the reaction induced by 1 mcg/kg of LSD-25.3.Pre-treatment of 10 subjects with 3 mg of BOL-148 for five days resulted in statistically significant attenuation of all aspects of the LSD reaction that were measured.4.The results are more compatible with the development of cross tolerance between BOL-148 and LSD-25 than they are with simple molecular competition between the two drugs.

Selection of patients for "elective" cholecystectomy.

To provide the general practitioner as well as the specialist with concise, readily available information on the latest, proved methods of treatment of conditions commonly encountered in an average practice, Postgraduate Medicine offers this department to its readers. It is not, of course, intended to present these discussions as the only acceptable therapeutic procedures to be used, but rather to offer simple regimens and recommendations based on the extensive experience of the physicians who prepared these summaries.