James C. Callaway

Human Psychopharmacology of Hoasca, A Plant Hallucinogen Used in Ritual Context in Brazil

A multinational, collaborative, biomedical investigation of the effects of hoasca (ayahuasca), a potent concoction of plant hallucinogens, was conducted in the Brazilian Amazon during the summer of 1993. This report describes the psychological assessment of 15 long-term members of a syncretic church that utilizes hoasca as a legal, psychoactive sacrament as well as 15 matched controls with no prior history of hoasca ingestion. Measures administered to both groups included structured psychiatric diagnostic interviews, personality testing, and neuropsychological evaluation. Phenomenological assessment of the altered state experience as well as semistructured and open-ended life story interviews were conducted with the long-term use hoasca group, but not the hoasca-naive control group. Salient findings included the remission of psychopathology following the initiation of hoasca use along with no evidence of personality or cognitive deterioration. Overall assessment revealed high functional status. Implications of this unusual phenomenon and need for further investigation are discussed.

Efficacy of dietary hempseed oil in patients with atopic dermatitis.

Background: Hempseed oil is a rich and balanced source of omega‐6 and omega‐3 polyunsaturated fatty acids (PUFAs). Anecdotal evidence indicated that dietary hempseed oil might be useful in treating symptoms of atopic dermatitis. Patients and methods: Dietary hempseed oil and olive oil were compared in a 20‐week randomized, single‐blind crossover study with atopic patients. Fatty acid profiles were measured in plasma triglyceride, cholesteryl and phospholipid fractions. A patient questionnaire provided additional information on skin dryness, itchiness and usage of dermal medications. Skin transepidermal water loss (TEWL) was also measured. Results: Levels of both essential fatty acids (EFAs), linoleic acid (18:2n6) and alpha‐linolenic acid (18:3n3), and gamma‐linolenic acid (GLA; 18:3n6) increased in all lipid fractions after hempseed oil, with no significant increases of arachidonic acid (20:4n6) in any lipid fractions after either oil. Intra‐group TEWL values decreased (p = 0.074), qualities of both skin dryness and itchiness improved (p = 0.027) and dermal medication usage decreased (p = 0.024) after hempseed oil intervention. Conclusions: Dietary hempseed oil caused significant changes in plasma fatty acid profiles and improved clinical symptoms of atopic dermatitis. It is suggested that these improvements resulted from the balanced and abundant supply of PUFAs in this hempseed oil.

Ayahuasca Preparations and Serotonin Reuptake Inhibitors: A Potential Combination for Severe Adverse Interactions

The Amazonian psychoactive plant beverage ayahuasca has attracted increasing interest in recent years. Little attention has been given, however, to potentially dangerous interactions with other drugs. In particular, the interaction between the potent monoamine oxidase-inhibiting harmala alkaloids in ayahuasca and the selective serotonin reuptake inhibitor (SSRI) class of antidepressants may induce a serotonin syndrome with potentially grave outcome. Caution is advised when combining ayahuasca with certain pharmaceutical drugs.

Platelet serotonin uptake sites increased in drinkers of ayahuasca

The binding of [3H]citalopram to the platelet 5-hydroxytryptamine (5-HT) transporter was measured in a group of healthy male drinkers ofayahuasca, a psychoactive sacrament indigenous to Amazonia, and a group healthy male controls. An increased number of binding sites (Bmax) in the platelets of ayahuasca drinkers was found, while the dissociation constant (Kd) remained the same for both groups. If indicative of neuronal 5-HT uptake activity, these results would suggest a decreased concentration of extracellular 5-HT, or a response to increased production and release of 5-HT. Such changes in 5-HT synaptic activity, in this case, should not be misinterpreted as an indication of developing neurological or psychiatric illness.

Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis.

Abstract A total of 32 Banisteriopsis caapi samples and 36 samples of Psychotria viridis were carefully collected from different plants on the same day from 22 sites throughout Brazil for phytochemical analyses. A broad range in alkaloid distribution was observed in both sample sets. All B. caapi samples had detectable amounts of harmine, harmaline and tetrahydroharmine (THH), while some samples of P. viridis had little or no detectable levels of N,N-dimethyltryptamine (DMT). Leaves of P. viridis were also collected from one plant and analyzed for DMT throughout a 24-hour cycle.

Determination of endocannabinoids in nematodes and human brain tissue by liquid chromatography electrospray ionization tandem mass spectrometry

A simple and highly sensitive liquid chromatography/tandem mass spectrometric (LC/MS/MS) method was developed to compare endogenous cannabinoid levels in nematodes and in brains of rats and humans, with and without prior exposure to ethanol. After liquid-liquid extraction of the lipid fraction from homogenized samples, a reversed-phase sub 2 μm column was used for separating analytes with an isocratic mobile phase. Deuterated internal standards were used in the analysis, and detection was made by triple quadrupole mass spectrometer with multiple reaction monitoring (MRM). Ionization was performed with positive electrospray ionization (ESI). The nematode Caenorhabditis elegans fat-3 mutant, that lacks the necessary enzyme to produce arachidonic acid, the biologic precursor to 2-arachidonoyl glycerol and anandamide, was used as an analyte-free surrogate material for selectivity and calibration studies. The matrix effect was further investigated by in-source multiple reaction monitoring (IS-MRM) and standard addition studies. Selectivity studies demonstrated that the method was free from matrix effects. Good accuracy and precision were obtained for concentrations within the calibration range of 0.4-70 nM and 40-11,000 nM for monitored N-acylethanolamides (NAEs) and acyl glycerols, respectively.

Various Alkaloid Profiles in Decoctions of Banisteriopsis Caapi

Abstract Twenty nine decoctions of Banisteriopsis caapi from four different sources and one specimen of B. caapi paste were analyzed for N,N-dimethyltryptamine (DMT), tetrahydroharmine (THH), harmaline and harmine. Other plants were also used in the preparation of these products, typically Psychotria viridis, which provides DMT. There were considerable variations in alkaloid profiles, both within and between sample sources. DMT was not detected in all samples. Additional THH may be formed from both harmine and harmaline during the preparation of these products. The alkaloid composition of one decoction sample did not change significantly after standing at room temperature for 80 days, but the initial acidic pH was neutralized by natural fermentation after 50 days.Twenty nine decoctions of Banisteriopsis caapi from four different sources and one specimen of B. caapi paste were analyzed for N,N-dimethyltryptamine (DMT), tetrahydroharmine (THH), harmaline and harmine. Other plants were also used in the preparation of these products, typically Psychotria viridis, which provides DMT. There were considerable variations in alkaloid profiles, both within and between sample sources. DMT was not detected in all samples. Additional THH may be formed from both harmine and harmaline during the preparation of these products. The alkaloid composition of one decoction sample did not change significantly after standing at room temperature for 80 days, but the initial acidic pH was neutralized by natural fermentation after 50 days.

Mass-spectrometric identification of anandamide and 2-arachidonoylglycerol in nematodes.

The purpose of the study was to see if nematodes (Caenorhabditis elegans, Caenorhabditis briggsae, and Pelodera strongyloides) produce endocannabinoids; i.e., anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG). In this study, AEA and 2‐AG were identified as endogenous products from nematodes by using electrospray‐ionization ion‐trap MS/MS (ESI‐IT‐MS) experiments operated in the positive‐ionization mode. Endocannabinoids were identified by product ion scan and concentrations were measured by triple quadrupole mass spectrometry in the multiple reaction monitoring mode (MRM). Both AEA and 2‐AG were identified in all of the nematode samples, even though these species lack known cannabinoid receptors. Neither AEA nor 2‐AG were detected in the fat‐3 mutant of C. elegans, which lacks the necessary enzyme to produce arachidonic acid, the fatty acid precursor of these endocannabinoids.

Endogenous cannabinoids in post-mortem brains of Cloninger type 1 and 2 alcoholics

The endogenous cannabinoid (EC) system has been recently implicated in several neuropsychiatric disorders. This study analyzed post-mortem brain regions of Cloninger type 1 (n=9) and 2 (n=8) alcoholics and non-alcoholic controls (n=10) for ECs by quantitative liquid chromatography with triple quadrupole mass spectrometric detection. A significant difference was found in anandamide (AEA) levels in nucleus accumbens (NAcc) between the three groups (p=0.047). AEA levels were significantly lower when compared to controls in both perigenual anterior cingulate (p=0.017) and frontal cortices (p=0.018) of type 1 alcoholics. Similar trends were observed for dihomo-gamma-linolenoyl ethanolamide and docosahexaenoyl ethanolamide, but not for 2-arachidonoylglycerol, palmitoyl ethanolamide, or oleoyl ethanolamide. Although preliminary, and from diagnostic groups with a relatively small number of subjects and substantially different mean ages for each group, these results suggest that the EC system may be hyperactive in type 2 alcoholics and hypoactive in type 1 alcoholics.

Fast and slow metabolizers of Hoasca

Abstract Harmine, a major alkaloid in ayahuasca (hoasca), is a selective and reversible inhibitor of the enzyme monoamine oxidase-A (MAO-A). It is also a selective inhibitor of the human cytochrome P450 isozyme 2D6 (CYP 2D6), which metabolizes harmine to a more hydrophilic derivative for eventual excretion. CYP 2D6 exhibits a wide range of polymorphisms in human populations, and variations in this enzymatic activity could account for differences in effects between individuals who use hoasca. This report broadly describes two subgroups of CYP 2D6 phenotypes—i.e., fast and slow metabolizers of harmine—in 14 experienced male members of the Uniāo do Vegetal (UDV) who received a standardized dosage of hoasca. To compensate for metabolic variations in their normal religious practice, the administered dose of hoasca is always determined by the presiding mestre, who is responsible for deciding the actual amount for each individual. This age-old method compensates for metabolic variations between individuals and v...Abstract Harmine, a major alkaloid in ayahuasca (hoasca), is a selective and reversible inhibitor of the enzyme monoamine oxidase-A (MAO-A). It is also a selective inhibitor of the human cytochrome P450 isozyme 2D6 (CYP 2D6), which metabolizes harmine to a more hydrophilic derivative for eventual excretion. CYP 2D6 exhibits a wide range of polymorphisms in human populations, and variations in this enzymatic activity could account for differences in effects between individuals who use hoasca. This report broadly describes two subgroups of CYP 2D6 phenotypes—i.e., fast and slow metabolizers of harmine—in 14 experienced male members of the Uniāo do Vegetal (UDV) who received a standardized dosage of hoasca. To compensate for metabolic variations in their normal religious practice, the administered dose of hoasca is always determined by the presiding mestre, who is responsible for deciding the actual amount for each individual. This age-old method compensates for metabolic variations between individuals and variations in both the alkaloid profile and strength of the hoasca.