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Explorations of two traditional, highly psychoactive herbal preparations-kava and ayahuasca-may offer psychiatrists insights into the mind and provide new psycho-pharmacological tools with which to combat mental disorders, according to panelists at an APA annual meeting symposium on herbal medicine in June.
The two preparations could not be more different in their effects, according to panelists Dennis McKenna, Ph.D., and Charles Grob, M.D. McKenna, who discussed kava, is director of ethnopharmacology at the Heffter Research Institute in Santa Fe, N.M., while Grob, who spoke on ayahuasca, is director of the division of child and adolescent psychiatry at Harbor-UCLA Medical Center and director of clinical research for the Heffter Research Institute. They collaborated on the ayahuasca study described below. The other primary collaborator for the ayahuasca study was J.C. Callaway, Ph.D., of the University of Kuopio, Finland.
Kava is a beverage prepared from the roots of Piper methysticum, a member of the pepper family.
It "has been used safely for thousands of years in Pacific Island cultures," McKenna said. Kava is used indigenously as a "social lubricant," he commented. "It fosters a mild state of relaxation" and is used "much the way that coffee or perhaps the cocktail is used in our own culture." It does not appear to cause addiction or dependency, is nontoxic, and is not stupefying, although like any psychoactive substance, it can be abused. In balance, however, "kava is safer than alcohol, prescription tranquilizers, or coffee," McKenna noted.
Kava extracts are now showing up in health food stores and pharmacies as dietary supplements. There is medical interest in its use as a safe and less costly herbal alternative to prescription tranquilizers and muscle relaxants, according to McKenna. The key active constituents are kavalactones. The effects of a specific root extract may vary depending on the relative proportions of the six major kavalactones, he explained. Although not sedative at normal doses, some varieties are more sedating at higher doses than others. At therapeutic doses, kava does not impair memory, cognition, attention, or reaction time, and some studies have shown that memory and cognition are slightly improved on kava versus placebo. It does not appear to interact additively with alcohol.
"These results are consistent with subjective reports of traditional users, who claim that kava produces a feeling of calm relaxation without interfering with mental clarity," McKenna said.
There are now 17 kava-containing products available as medicinals in Europe, and the German equivalent of the Food and Drug Administration has issued a positive report on kava.
The pharmacology of kava is unclear, but anxiolytic efficacy may be due to modulation of gamma aminobutyric acid (GABA) receptors, a property shared with benzodiazepines, although kava compounds do not bind to the same sites as benzodiazepines, he noted.
Kava compounds reduce action-potential conductance and block ion-receptor channels in muscle membranes, reducing muscle contractility, a likely explanation of the herb's muscle-relaxant effects. Kava's analgesic effects are not modulated by opioid mechanisms, animal studies have shown. Other research suggests a neuro-protective effect in reducing the size of ischemically induced cerebral infarcts. Although not sedative at normal doses, kava appears to work well in combination with the herb valerian for inducing sleep.
Ayahuasca is a hallucinogenic mixture originally used only by indigenous Amazonian tribes, but now used more widely as a legal, religious sacrament throughout Brazil, explained Grob. It was legalized for ritual use in 1987. Ayahuasca's pharmacological action depends on synergy between the active alkaloids in its two plant constituents: those contained in the bark of Banisteriopsis caapi, which are potent monoamine oxidase (MAO) inhibitors, and the potent, short-acting hallucinogen dimethyltryptamine (DMT) contained in the leaves of Psychotria viridis. Absent the MAO inhibitor, DMT is orally inactive, Grob noted. It is "a very sophisticated plant psychopharmacology, which the native people somehow happened upon," he commented.
Intrigued by earlier reports of ritual use of ayahuasca, Grob, McKenna, and colleagues arranged to visit a contemporary church of the Uniao de Vegetal, which employs the potion as a sacrament.
The researchers went to Manaus in the Amazon, where they recruited 15 long-term ritual ayahuasca users and 15 nonusing controls. Participants were assessed using both psychological and physiological measures. The findings were published in the Journal of Nervous and Mental Disease, Psychopharmacology, Journal of Analytical Toxicology, and Journal of Ethno-pharmacology.
Prior to their entry to the ayahuasca church, 11 of the 15 had alcohol abuse problems, eight had been nicotine addicts, and four had problems with cocaine or amphetamine, Grob found.
"All of this pathology remitted in their 10-year-plus involvement with this church," he commented.
The ayahuasca users had gone from being dysfunctional to being "upstanding citizens of the community with very strong family values," he noted. Collaborator McKenna commented that they were "just like the Mormon church, only on psychedelics."
The church members believed that "having a ritual structure was absolutely essential to achieving positive outcomes and expressed great concern that individuals taking [ayahuasca] without ritual structure" might be harmed.
Recently Grob and colleagues began collaborating with substance abuse experts from the medical school in Sao Paulo on the potential use of ayahuasca to fight cocaine addiction. The Brazilian narcotics commission (equivalent to the United States Drug Enforcement Administration) has asked for help. "They're overwhelmed by the crack epidemic throughout Brazil" and "feel helpless," said Grob. The narcotics commissioners, who cooperated in the 1987 legalization of ayahuasca for ritual use, had noticed that many of the ayahuasca users had previously had substance abuse problems that remitted after their involvement with the ayahuasca church, said Grob. "They feel that there may be some potential here."
Ayahuasca was found to be relatively safe because of its minimal impact on cardiovascular function and other physiological processes. Receptor binding studies found an increased density of serotonin receptors in platelets of long-term ayahuasca users versus controls. Neuro-psychological testing of memory and concentration found "no evidence of deterioration compared with normal controls "and "some indication of better function among the ayahuasca-using subjects," according to Grob.
Subjects told Grob they were not surprised by the findings, as they thought their powers of memory and concentration had improved markedly since they started ritual use of ayahuasca.
The apparent increased density of serotonin receptor sites with long-term use raises intriguing questions for psychopharmacology. "Might this periodic utilization of a powerful serotonergic agonist be the makings of an antidepressant with greater efficacy? I've been informed recently that one of the major pharmaceutical companies is undertaking laboratory studies looking at basic animal models" of ayahuasca's actions, said Grob.
Plant hallucinogens can help psychiatry learn about "mind, about brain, about mental illness, perhaps provide clues to treatment. I do think we need to be attentive to the people who have learned to use this within the context of their own indigenous cultures."
Although only a pilot study, it has demonstrated the feasibility of such research, said Grob. "This is a fascinating phenomenon. It has been ignored by modern psychiatry," he added. Thirty years ago, hallucinogen research was seen as "a very exciting area in psychiatry," but research was put on hold after a backlash related to the excesses of the 1960s. The question now is "can we go back to studying these fascinating compounds. . .without falling into the traps that prior generations of researchers fell into?"
Relevant Web sites include those of the Heffter Research Institute at McKenna's e-mail address is djmckenna@aol.com; Grob's e-mail address is grob@AFP76.humc.edu.
-R.B.K.