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Psychiatric Times. Vol. 15 No. 12
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Clinical Trials Indicate Value of Herbal Medicines

By Kenneth J. Bender, Pharm.D., M.A. | December 1, 1998

Researching Hallucinogens

In seeking therapeutic herbal medicines, researchers are increasingly examining how indigenous peoples utilize botanicals, including hallucinogenic substances.

Charles Grob, M.D., associate professor of psychiatry at the University of California, Los Angeles (UCLA) School of Medicine, and director of the Division of Child and Adolescent Psychiatry at Harbor-UCLA Medical Center, indicated in his presentation, "Plant Entheogens as Medicine," that formal psychiatric research with hallucinogens has recently resumed after a 25-year period of "virtual prohibition" on such scientific inquiry.

Grob attributes the quarter century absence of research with hallucinogens to a backlash response to unscientific experimentation and illicit use of hallucinogens in the 1960s. He pointed out, however, that suppression of research with these substances has earlier precedents.

"The shamanistic use of hallucinogenic plants as agents designed to facilitate healing, acquire knowledge and enhance societal cohesion [was] brutally repressed in both the Old and New Worlds by the progenitors of our own contemporary Euro-American cultures, often with the complicity of the medical professions [Grob, 1994]."

The recent improved support and attitude toward this field of research was marked by a technical meeting of the National Institute of Drug Abuse in 1992, attended by Grob. It was the consensus of that meeting that it is now appropriate, with the technology available to perform functional brain imaging and neuroendocrine and neuroreceptor assessments, to progress from animal studies to, again, studies of the effects of these substances in humans.

"The strategy of pursuing such biological investigations will likely not only yield valuable new information in the neurosciences," Grob has written, "but facilitate the relegitimization of human research with hallucinogens and ultimately become prelude to the re-exploration of their effects on perception, cognition and emotion [Grob, 1994]."

Grob described his own recent investigation of the botanical hallucinogen mixture hoasca, also known as yagé and daime (Grob et al., 1996). The hallucinogen is brewed from a woody vine the Mazan and Zaparo Indians call ayahuasca (Quechua for "vine of the souls" or "vine of the dead") and the leaves of the hallucinogenic tryptamine-containing plant Psychotria viridis (chacarona plant). The botanical designation of ayahuasca (Banisteriopsis caapi) was originally documented by English botanist Richard Spruce in the mid-1800s, who also identified Hevea, the genus of the rubber tree, and Cinchona calisaya, the source for quinine(Drug information on quinine). Analysis of ayahuasca has revealed the psychoactive beta-carboline alkaloids harmine, harmaline and tetrahydroharmine; and N,N-dimethyltryptamine (DMT) is yielded from the Psychotria viridis(Callaway et al., 1996).

The combination of ayahuasca and Psychotria viridis by the Indians of the Amazon-like the addition of Piper longum or Piper nigrum to an active herb in Ayurvedic medicine as described in the August article-is another example of an ancient, empirical enhancement of pharmacological effect by drug metabolism inhibition.

James Callaway, Ph.D., of the department of pharmacology and toxicology, University of Kuopio, Finland, has noted that DMT from the Psychotria is a short-acting psychotropic agent when administered parenterally, but it is not orally active because of its degradation by MAOA in the gastrointestinal tract. When combined with ayahuasca, however, the harmala alkaloids serve to inhibit the activity of MAOA, and psychoactive effects are exerted by the orally administered DMT (Callaway et al., 1996).

Grob's investigation of the use of hoasca among peoples of the Brazilian Amazon was sponsored in part by the Heffter Research Institute, and was conducted with McKenna, Callaway and other colleagues, including medical faculty in Brazil from the Centro De Estudos Medicos, São Paulo, and psychiatry faculty from the Departamento Psiquiatria of the Universidade Estudial do Rio De Janeiro and of the Escola Paulista de Medecina, São Paulo (Grob et al., 1996).

Grob had explained the rationale for such research earlier, in the Yearbook of Ethnomedicine: "If we are to develop optimal research design for evaluating the therapeutic utility of hallucinogens, it will not be sufficient to adhere to strict standards of scientific methodology alone. We must also pay heed to the examples provided us by such successful applications of the shamanic paradigm [Grob, 1994]."

Grob described the application of a rigorous research protocol, including blood draws for pharmacokinetic studies, in the primitive setting of the Amazon as "a fascinating experience." The project was featured in the British Broadcasting Corporation documentary "Psychedelic Science," which recently aired in the United States on the Arts and Entertainment cable channel in their "Unexplored Mysteries" series.

The researchers selected 15 long-term members of the syncretic church, Uninão do Vegetal (UDV), chosen randomly from among volunteers in the town of Manaus. These individuals had utilized ayahuasca in the context of their church rituals a minimum of twice monthly, and some as often as several times per week. Grob noted that their adherence to the rituals necessitated abstinence from all other psychoactive substances, including alcohol(Drug information on alcohol), tobacco, marijuana, cocaine and amphetamines. An additional 15 subjects who did not consume ayahuasca, but were demographically matched, served as controls.

The investigators applied a battery of tests to assess past and current psychological functioning, including the Composite International Diagnostic Interview, the Tridimensional Personality Questionnaire and the WHO-UCLA Auditory Verbal Learning test of neuropsychological functioning. The users of the hallucinogen also completed the Hallucinogen Rating Scale.

Grob and colleagues reported that despite a number of the subjects having had alcohol, depressive or anxiety disorders prior to their participation in the church ritual use of the hallucinogen, "all disorders had remitted without recurrence after entry into the UDV." The researchers qualify this finding as preliminary and tentative, and acknowledge the salutatory effects of support from religious affiliation. Nevertheless, they opine, "It is not inconceivable that the long-term use of the hoasca itself may have had a direct positive and therapeutic effect on our subjects' psychiatric and functional status."

Grob commented to Psychiatric Times, "We think this should be a reputable area of investigation for contemporary medical psychiatric researchers...it is possible to research this area in an objective, scientific manner and come back with valuable information."

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References
1. Almeida JC, Grimsley EW (1996), Coma from the health food store: interaction between kava and alprazolam. Ann Int Med 125(11):940-941. Letter.
2. Callaway JC, Raymon LP, Hearn WL et al. (1996), Quantification of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca. J Anal Toxicol 20(6):492-497.
3. Grob CS (1994), Psychiatric research with hallucinogens: what have we learned? Yearbook of Ethnomedicine, Ratsch C, Baker J, eds. Berlin: Verlagfür Wissenschaft und Bildung (VWB), pp 91-112.
4. Grob CS, McKenna DJ, Callaway JC et al. (1996), Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. J Nerv Ment Dis 184(2):86-94.
5. Heinze HJ, Münthe TF, Steitz J, Matzke M (1994), Pharmacopsychological effects of oxazepam and kava extract in a visual search paradigm assessed with event-related potentials. Pharmacopsychiatry 27(6):224-230.
6. Kinzler E, Krömer J, Lehmann E (1991), [Effect of a special kava extract in patients with anxiety-, tension-, and excitation-states of non-psychotic genesis. Double-blind study with placebos over four weeks]. Arzneimittelforschung 41(6):584-588.
7. Linde K, Ramirez G, Mulrow CD et al. (1996), St. John's wort for depression-an overview and meta- analysis of randomized clinical trials. BMJ 313(7052):253-258. See comments.
8. Müller WE, Rolli M, Schäfer C, Hagner U (1997), Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry 30(suppl 2):102-107.
9. Münte TF, Heinze HJ, Matzke M, Steitz J (1993), Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related potentials in a word recognition task. Neuropsychobiology 27(1):46-53.
10. Norton SA (1998), Herbal medicines in Hawaii from tradition to convention. Hawaii Med J 57(1):382-386.
11. Volz HP, Kieser M (1997), Kava-kava extract WS 1490 versus placebo in anxiety disorders-a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry 30(1):1-5.
12. Warnecke G (1995), Psychosomatische dysfunktionen imn weiblichen klimakteriu. Klinische wirksamkeit und verträglichkeit von kava-extgract WS 1490. Fortschr Med 109:119-122.


 
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