Experimental Psychiatry. V - Psilocybine, a New Psychotogenic Drug

Psilocybine was supplied as 2-mg tablets with a sweet taste that dissolved relatively slowly under the tongue. The researchers gave single sublingual doses of 5 to 10 mg to four male volunteers whose pre-experimental physical and mental status was well known to the investigators. Three of the volunteers had prior experience with psychotropic drugs in experimental settings; for one volunteer it was the first such experience. The sessions were conducted in a quiet room with venetian blinds drawn at the Massachusetts Mental Health Center. Each session was observed by one psychiatrist and three psychologists. The pilot study focused on observing mental and behavioural changes; a small battery of psychological tests (including block design tasks) was administered to provide objective data, and neurological changes were recorded if noted. The extracted text does not report further inclusion/exclusion criteria, randomisation, blinding, or formal analytic methods, consistent with a small open observational experiment.

All four subjects showed activity attributable to the drug. Effects began between 30 and 45 minutes after administration, reached an acme at about one hour, and persisted for about three to four hours. Return to pre-experimental state was gradual over approximately 16 hours, although subjects reported feeling competent to resume routine activities after six to eight hours. No untoward aftereffects were observed or reported. Psychological effects were generally described as mild but variable between subjects. All four exhibited increased irritability and attempts at overcontrol, yet remained fully oriented to time, place and person. None of the four subjects experienced true hallucinations; one subject reported illusions consisting of light rays on the wall that assembled into geometric patterns (described as a spider web) with only slight distortion from objective perception. The authors note that in earlier reports true hallucinations were rare in normal subjects and were reported by Delay mainly in a single melancholic patient. Mood changes occurred in all participants and ranged from euphoria to dysphoria. Behavioural responses diverged: two subjects felt relaxed and sleepy with difficulty keeping their eyes open, while the other two were restless, wanting to move and active; one of the latter described feeling jumpy, slightly manic and tense. An example of task impairment was a musician who felt buoyant and compelled to play piano but was unable to sustain tempo, missed notes and abandoned playing after less than ten minutes because of annoyance with his performance. Speech varied between slow/slurred and rapid (push of speech). Thinking appeared logical but slowed; the researchers did not observe fragmentation or disconnection of thought. All subjects showed disturbed concentration and attention. Performance on perceptual tasks was moderately disturbed, and time perception was reported as either too fast or too slow in most subjects. One subject experienced depersonalisation, reporting feelings of extreme height and smallness and a sensation that his legs were detached. Somatic symptoms included lightheadedness, nausea, pressure in the head, photosensitivity and a sensation of leg weakness described as rubberlike or waxy. On block design psychometric testing, all four subjects showed marked difficulty and exhibited what the authors cite as Kurt Goldstein’s "catastrophic response." The degree of impairment during the peak drug reaction was reported to be considerably greater than that seen in comparable volunteers during LSD experiments.

The authors interpret their findings as confirming that psilocybine is an active psychotogenic chemical similar in qualitative effects to LSD and mescaline. They present an approximate potency ranking by dose required to produce observable effects in adults: LSD at about 70 micrograms, mescaline about 500,000 micrograms, and psilocybine in the range of 5,000 to 10,000 micrograms (5–10 mg). R. and colleagues emphasise that, in their and Delay’s experiments in normal subjects, true hallucinations were uncommon. They note that Delay and co-workers reported a single case of a melancholic patient who experienced terrifying hallucinations. The authors highlight a range of factors that materially influence experimental outcomes: personality and attitudes of observers, the artificiality of the experimental setting compared with native ceremonial contexts, environmental conditions (lighting, temperature, humidity), dosage and route of administration, purity of the compound (raising the possibility that plant impurities could contribute to dramatic effects reported anecdotally), timing and duration of observation, subjects’ emotional state and expectancy, prior drug experience, and the personality and motives of participants. These considerations are presented by the authors as caveats that complicate direct comparison across studies and settings and that should be taken into account in future experimental work. The extracted text does not present additional formal limitations, statistical analyses or recommendations beyond these noted influences on outcome.