Effects of mescaline and lysergic acid (d-LSD-25)

The researchers studied two related series of patients. For mescaline, 59 patients with schizophrenia (24 males, 35 females) received synthetic mescaline sulfate intravenously at dosages of 0.4 to 0.6 gm. These patients had been closely observed prior to drug administration, either through prior psychotherapeutic contact or frequent clinical observation, so baseline symptomatology was well known. The 59 patients were divided into three clinical groups: (1) 17 patients described as having the pseudoneurotic form of schizophrenia (with obsessive-compulsive, phobic, anxiety-tension-depressive or related features); (2) 26 patients characterised as paranoid, catatonic, hebephrenic or mixed/unclassified, with 17 reported as showing no deterioration and 9 slight deterioration; and (3) 16 patients who were definitely deteriorated (moderately severe to severe), including catatonic, paranoid and mixed types. A separate but overlapping series of 21 schizophrenic patients were studied with lysergic acid (d-LSD-25). Nineteen of these 21 had also previously received mescaline (16 by the intravenous route and 4 by the oral route; one patient received both routes at different times). Lysergic acid doses varied from 10 gamma to 120 gamma; the researchers noted that mental changes were most reliable at doses of 60 gamma or more. Observations recorded for both drugs included autonomic/vegetative, motor and sensory effects; disturbances of perception (hallucinations, illusions, distortions of body image); thought and language changes; mental content that emerged under the drug; and emotional alterations. No formal statistical analysis methods are described in the extracted text. Reporting emphasises counts of patients experiencing particular phenomena, qualitative comparisons between drugs and patient groups, time course of effects, and reproducibility on repeated administrations. Route of administration and dose are highlighted as factors likely affecting intensity and timing of responses.

Under mescaline, a broad range of autonomic and vegetative disturbances were common across patients: pupillary dilatation, nausea, vomiting, chilliness, headache, tremor, flushing, numbness of hands, a sense of heat, unsteadiness, hyperacusis, reduced blood pressure and occasional bradycardia. These symptoms typically began about one-half to one hour after administration, peaked around 2 hours, and declined so that the overall action lasted 4 to 6 hours. Hallucinations were frequent. In the pseudoneurotic first group (n=17) 15 patients had visual hallucinations, 8 auditory, and 2 olfactory. In the second group (n=26) 22 had visual, 8 auditory, 3 olfactory, 1 haptic and 1 gustatory hallucinations. In the third, more deteriorated group (n=16) 7 had visual, 2 auditory and 1 olfactory hallucinations. Visual phenomena predominated in schizophrenic patients and matched the form of visual hallucinations reported in normal subjects under mescaline, whereas auditory hallucinations were less common than the high incidence of auditory hallucinations seen in drug-free schizophrenics. Emotional changes under mescaline most commonly involved increased anxiety; hostility was frequently observed. Depression occurred less commonly and when present tended to be agitated rather than retarded depression. Patients often exhibited concern with pre‑existing symptomatology, evasiveness, vagueness or denial—features that were frequently present before drug administration and were often reinforced by the drug. In some cases, previously present obsessive-phobic symptomatology diminished under the drug. Paranoid manifestations were common: they were amplified in patients with prior paranoid trends and also appeared de novo in some patients, notably among those classified as pseudoneurotic. Comparisons with normal subjects indicated both similarities and differences. Vegetative changes and visual perceptual alterations (geometric figures, colours, distortions of body image) were similar in form to those in normals, as were disturbances of time sense, feelings of unreality and speech/thought changes. However, euphoria—prominent in normal subjects—was infrequent in schizophrenic patients. Sexual content in verbal productions was more frequent in schizophrenic patients than in normals. Overall, the researchers judged that reactions in schizophrenics were quantitatively more intense, with greater anxiety and disorganisation, although they stopped short of asserting qualitative identity with spontaneous schizophrenia. Lysergic acid (d-LSD-25) produced vegetative and perceptual disturbances similar in character to mescaline but generally of lesser intensity and less diffuseness than intravenous mescaline; the lysergic acid responses were comparable in intensity to oral mescaline. Symptoms with lysergic acid occurred 30 to 60 minutes after ingestion. Visual hallucinations were reported at a significantly lower frequency with lysergic acid than with mescaline; other perceptual disturbances occurred at similar rates. Disturbances of time sense and feelings of unreality were reported but were generally less intense with lysergic acid. Thought and language disturbances occurred with lysergic acid when doses exceeded 10 gamma and were comparable to those seen with mescaline. The most frequent subjective complaint with lysergic acid was impaired concentration or haziness of mind, sometimes described as a sedative-like effect; some patients reported relief or a perceived therapeutic aspect of that sedation. Emotional responses to lysergic acid varied: seven patients relaxed or showed euphoria (occasionally mixed with anxiety), six were depressed with retardation, three alternated euphoria and depression, six had predominantly anxious reactions, and a small number showed no significant effect. Frank paranoid delusional constellations were less frequent with lysergic acid than with mescaline. Two patients showed intensification of catatonic signs and one paranoid patient had increased paranoid attitude under lysergic acid. Across both drugs, the better-preserved (pseudoneurotic and undeteriorated/moderately deteriorated) patients tended to verbalise and show more overt emotional reactions; severely deteriorated patients often failed to verbalise and could become catatonically withdrawn despite physiologic and perceptual alterations being as intense as in less deteriorated groups. Repeated administrations produced relatively consistent patterns in most patients: paranoid attitudes, silliness, and schizophrenic thought disorder were often reproducible, while anxiety, tension and unreality feelings sometimes decreased on repetition; occasionally more euphoria was observed with repeat dosing. The researchers reported that mescaline could "reactivate the psychosis in every detail" after topectomy in patients who had undergone such surgery, although in some cases the quantitative magnitude of the response was reduced.

The researchers interpret their findings as showing that both mescaline and lysergic acid can magnify pre-existing schizophrenic structures and produce schizophrenic‑like experiences in normal subjects, but that drug-provoked states in normals are not identical to endogenous schizophrenia. In schizophrenic patients the drugs tended to reinforce existing symptomatology—particularly paranoia, anxiety and thought‑language disturbances—and to produce more intense and disorganising reactions than in normals. The authors emphasise quantitative differences (greater intensity and disorganisation in patients) and reserve judgement on whether qualitative differences exist. They note important distinctions between the two drugs in their sample: intravenous mescaline produced more rapid, massive and diffuse symptoms (including more frequent visual hallucinations and more diffuse somatic disturbances) compared with orally administered lysergic acid, which produced less intense and less diffuse effects akin to oral mescaline. The researchers acknowledge that route of administration and dose are important determinants of the clinical picture and that some differences between drugs may reflect these factors rather than intrinsic pharmacological differences. The authors discuss potential clinical uses cautiously. They have employed the drugs mainly as investigative tools to study psychosis and personality structure under drug stress and suggest possible roles in diagnosis, prognosis and psychotherapy, but conclude that available evidence does not support reliable clinical use for these purposes at present. They report that mescaline can precipitate overt psychosis in some patients with pseudoneurotic schizophrenia and suggest that deteriorated and regressed patients may respond differently, indicating possible prognostic value. Nonetheless, they call for further systematic investigation in larger samples to determine therapeutic or diagnostic utility. Limitations and uncertainties acknowledged in the text include variability of response on repeated administrations, dose‑ and route‑related differences in intensity (for example, lysergic acid effects being less reliable below 60 gamma), and the difficulty of distinguishing drug-induced psychotic features in normals from true psychotic reactions in pseudoneurotic patients. The researchers recommend more extensive research to clarify these issues and to establish clinical usefulness, while stressing that they have used the drugs primarily for investigative, not therapeutic, purposes.