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Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens

Nichols, D. E. (1986). Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. Journal of psychoactive drugs, 18(4), 305-313. http://dx.doi.org/10.1080/02791072.1986.10472362
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Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca

Abstract

Ayahuasca is a hallucinogenic beverage derived by boiling the bark of the Malpighiaceous liana Banisteriopsis caapi together with the leaves of various admixture plants, viz. Psychotria viridis, Psychotria carthagenensis, or Diplopterys cabrerana. B. caapi contains harmine, harmaline, and tetrahydroharmine while the admixtures contain N,N-dimethyltryptamine (DMT). DMT, a potent hallucinogen, is inactive orally due to degradation by visceral monoamine oxidase (MAO). The β-carbolines, however, are highly active reversible inhibitors of MAO and may protect the DMT from deamination by MAO and render it orally active. This mechanism has been proposed to underlie the oral activity of ayahuasca but has not been experimentally confirmed. In the present study the constituents of the admixture plants and the alkaloids of eight ayahuasca samples from Peru were qualitatively and quantitatively analyzed using two-dimensional thin-layer chromatography (TLC), high pressure liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS).

Several B. caapi cultivars were quantitatively compared for variations in alkaloid content. Three admixture plants used rarely in the manufacture of ayahuasca were also screened for alkaloids. A selected sample of β-carbolines were screened for activity as MAO inhibitors using an in vitro assay system, and structure/activity relationships were compared. Inhibition observed with single compounds was compared with the activity of selected samples of ayahuasca which were screened in the system and also with the activity of mixtures of β-carbolines. The levels of DMT and β-carbolines found in the ayahuasca samples examined in the present study were an order of magnitude greater than the levels reported in a previous study. Ayahuasca was found to be an extremely effective inhibitor of MAO in vitro and the degree of inhibition was directly correlated with the concentration of MAO-inhibiting β-carbolines. Inhibition experiments using mixtures of β-carbolines indicated that their effects in combination are additive, rather than synergistic or antagonistic. Implications of the results in understanding the pharmacology of ayahuasca are discussed.

McKenna, D. J., Towers, G. N., & Abbott, F. (1984). Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and β-carboline constituents of ayahuasca. Journal of ethnopharmacology, 10(2), 195-223. 10.1016/0378-8741(84)90003-5
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LSD-assisted psychotherapy in patients with terminal cancer

Abstract

The paper describes the results of a clinical study exploring the potential of a complex psychotherapeutic program utilizing psychedelic compounds to alleviate the emotional and physical suffering of cancer patients. A total of 60 cancer patients participated in this experimental study. In 44 of these patients, LSD (200-500 ug per os) was administered as an adjunct to psychotherapy; in 19 patients, a new psychedelic compound, dipropyltryptamine (DPT) was administered (60-105 mg i.m.). Three of these patients received both LSD and DPT administered on different sessions.

The therapeutic results were assessed by means of a rating scale reflecting the degree of the patients’ depression, psychological isolation, anxiety, difficulty in management, fear of death, and pain. The ratings were done by attending physicians, nurses, family members, LSD therapists and cotherapists, and independent raters. In addition, the amount of narcotics required in the management of the patient was measured before and after the psychedelic sessions.

Systematic rating was carried out in a group of 31 cancer patients treated by LSD. The comparison of the means of individual ratings from pre- to posttreatment showed significant improvement in all the measured parameters for most of the raters. There was a definite reduction of the narcotic medication; it did not, however, reach the level of statistical significance. The pre- to post-treatment comparison of the global indexes used as gross indicators of the degree of emotional and physical distress, indicated that approximately 29 % of the patients showed dramatic improvement, and another 41.9 % moderate improvement, with 22.6 % essentially unchanged. In 6.4 % of the patients, global indexes showed a decrement in the post therapy ratings.

Grof, S., Goodman, L. E., Richards, W. A., & Kurland, A. A. (1972). LSD-assisted psychotherapy in patients with terminal cancer. International pharmacopsychiatry, 8(3), 129-144.
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LSD-Assisted Psychotherapy in Patients with Terminal Cancer

Abstract

The paper describes the results of a clinical study exploring the potential of a complex psychotherapeutic program utilizing psychedilic compounds to alleviate the emotional and physical suffering of cancer patients. A total of 60 cancer patients participated in this experimental study. In 44 of these patients, LSD (200-500 μg per os) was administered as an adjunct to psychotherapy; in 19 patients, a new psychedelic compound, dipropyltryptamine (DPT) was administered (60-105 mg i.m.). Three of these patients received both LSD and DPT administered on different sessions. The therapeutic results were assessed by means of a rating scale reflecting the degree of the patients’ depression, psychological isolation, anxiety, difficulty in management, fear of death, and pain. The ratings were done by attending physicians, nurses, family members, LSD therapists and cotherapists, and independent raters. In addition, the amount of narcotics required in the management of the patient was measured before and after the psychedelic sessions. Systematic rating was carried out in a group of 31 cancer patients treated by LSD. The comparison of the means of individual ratings from pre to posttreatment showed significant improvement in all the measured parameters for most of the raters. There was a definite reduction of the narcotic medication; it did not, however, reach the level of statistical significance. The pre to posttreatment comparison of the global indexes used as gross indicators of the degree of emotional and physical distress, indicated that approximately 29% of the patients showed dramatic improvement, and another 41.9% moderate improvement, with 22.6% essentially unchanged. In 6.4% of the patients, global indexes showed a decrement in the posttherapy ratings.
Grof, S., Goodman, L. E., Richards, W. A., & Kurland, A. A. (1973). LSD-assisted psychotherapy in patients with terminal cancer. International pharmacopsychiatry8, 129-144., 10.1159/000467984
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DPT as an adjunct in psychotherapy of alcoholics.

Abstract

The usefulness of dipropyltryptamine (DPT) as an adjunct to psychedelic therapy was explored in a pilot study carried out on 51 alcoholic patients from the Alcoholic Rehabilitation Unit at Spring Grove State Hospital. The evaluation of the results was based on the comparison of pre- and posttreatment results of a battery of psychological tests and of pretreatment and follow-up ratings of an independent team of social workers. The psychological tests involved the Minnesota multiphasic personality inventory (MMPI), Personal orientation inventory (POI), Raven progressive matrices, Psychiatric evaluation profile (PEP), and Benton visual retention test. The social history questionnaire used by the social workers for assessment of the patients’ adjustment consisted of 0-10-point scales measuring residential, occupational and interpersonal adjustment, abstinence, and global adjustment.
Grof, S., Soskin, R. A., Richards, W. A., & Kurland, A. A. (1973). DPT as an adjunct in psychotherapy of alcoholics. International pharmacopsychiatry8, 104-115., 10.1159/000467979
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LSD-assisted psychotherapy and the human encounter with death

Abstract

INTRODUCTION: My own experience with Maria convinced me that the living can do a great deal to make the passage easier for the dyingJ to raise the most purely physiological act of human existence to the level of consciousness and perhaps even of spirituality.

Aldous Huxley wrote these words after being with his first wife as she died of cancer in 1955. During her final hours, he employed a hypnotic technique to remind her of spontaneous peak experiences she had known during her life, thereby seeking to guide her toward similar states of consciousness as the death process occurred. In his novel/sland, he describes a similar scene during the death of his character Lakshmi. Also in this novel, he writes of the “mokshamedioine” that gives inhabitants of the island a mystical vision that frees them from the fear of death and enables them to live more fully during their everyday lives. To those who knew Aldous Huxley and have read his works (Huxley, 1963a,b), there is no doubt that, in Huxley’s mind, £cmokshamedieine” was a psychedelic oompound similar to mescaline, psilocybin, and LSD. The seriousness with which he envisaged this futuristic scene is well portrayed by his second wife, Laura) in her description of Huxley’s request for LSD a few hours before he himself died of cancer in 1963 (Huxley, 1968).

 Richards, W., Grof, S., Goodman, L., & Kurland, A. (1972). LSD-assisted psychotherapy and the human encounter with death. Journal of Transpersonal Psychology, 4(2), 121-150.

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Attenuation and anticipation: A therapeutic use of lysergic acid diethylamide

Abstract

Theoretical reasons for the use of LSD as an analgesic agent are elaborated. In a series of 128 patients the analgesic action of LSD is further confirmed, and the undesirable pharmacologic effects are discussed. The relative safety of the drug for that use is demonstrated, and further study is recommended.

Kast, E. (1967). Attenuation of anticipation: a therapeutic use of lysergic acid diethylamide. Psychiatric Quarterly, 41(4), 646-657. http://dx.doi.org/10.1007/BF01575629
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Psychedelic Agents in Creative Problem-Solving: A Pilot Study

Abstract

Based on the frequently reported similarities between creative and psychedelic (drug-induced, consciousness-expansion) experiences, a preliminary study was conducted to explore the effects of psychedelic agents (LSD-25, mescaline) on creative problem-solving ability. Twenty-seven professionally employed males were given a single psychedelic experience in 1 of 7 small groups (ns = 3 or 4) following extensive selection and preparatory procedures. This drug-induced problem-solving session was carefully structured with particular focus on establishing Ss’ expectancies and a psychosocial milieu conducive to creative activity. Tentative findings based on tests of creativity, on subjective reports and self ratings, and on the utility of problem solutions suggested that, if given according to this carefully structured regimen, psychedelic agents seem to facilitate creative problem-solving, particularly in the “illumination phase.” The results also suggest that various degrees of increased creative ability may continue for at least some weeks subsequent to a psychedelic problem-solving session.

Harman, W. W., McKim, R. H., Mogar, R. E., Fadiman, J., & Stolaroff, M. J. (1966). Psychedelic Agents in Creative Problem-Solving: A Pilot Study. Psychological Reports, 19, 211-227.
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The subjective experience of time during lysergic acid diethylamide (LSD-25) intoxication

Abstract

A brief review of the literature in relation to time disorder and LSD-25 is given. Twenty nine patients were studied as regards their time experiences under LSD-25. Eight patients reported an altered time experience following the initial administration of the drug. Twelve patients who had not developed a time disturbance in their initial administration, received LSD-25 a second time at increased dosage, 5 of these patients then experienced a time disturbance.

There was a tendency for time disorder to be associated with visual perceptual changes and for it to occur in the non-schizophrenics. Time disorder was considered to be a non-specific response. Recent views on the nature and genesis of time disorders are discussed.

Kenna, J. C., & Sedman, G. (1964). The subjective experience of time during lysergic acid diethylamide (LSD-25) intoxication. Psychopharmacologia5(4), 280-288., 10.1007/BF02341260
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