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1.
J Ethnopharmacol ; 323: 117710, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38184028

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ayahuasca (AYA) is a psychedelic brew used in religious ceremonies. It is broadly used as a sacred medicine for treating several ailments, including pain of various origins. AIM OF THE STUDY: To investigate the antinociceptive effects of AYA and its mechanisms in preclinical models of acute and chronic pain in mice, in particular during experimental neuropathy. MATERIALS AND METHODS: The antinociceptive effects of AYA administered orally were assessed in the following models of pain: formalin test, Complete Freund's Adjuvant (CFA)-induced inflammation, tail flick test, and partial sciatic nerve ligation model of neuropathic pain. Antagonism assays and Fos immunohistochemistry in the brain were performed. AYA-induced toxicity was investigated. AYA was chemically characterized. The antinociceptive effect of harmine, the major component present in AYA, was investigated. RESULTS: AYA (24-3000 µL/kg) dose-dependently reduced formalin-induced pain-like behaviors and CFA-induced mechanical allodynia but did not affect CFA-induced paw edema or tail flick latency. During experimental neuropathy, single treatments with AYA (24-3000 µL/kg) reduced mechanical allodynia; daily treatments once or twice a day for 14 days promoted consistent and sustained antinociception. The antinociceptive effect of AYA (600 µL/kg) was reverted by bicuculline (1 mg/kg) and methysergide (5 mg/kg), but not by naloxone (5 mg/kg), phaclofen (2 mg/kg), and rimonabant (10 mg/kg), suggesting the roles of GABAA and serotonergic receptors. AYA increased Fos expression in the ventrolateral periaqueductal gray and nucleus raphe magnus after 1 h, but not after 6 h or 14 days of daily treatments. AYA (600 µL/kg) twice a day for 14 days did not alter mice's motor function, spontaneous locomotion, body weight, food and water intake, hematological, biochemical, and histopathological parameters. Harmine (3.5 mg/kg) promoted consistent antinociception during experimental neuropathy. CONCLUSIONS: AYA promotes consistent antinociceptive effects in different mouse models of pain without inducing detectable toxic effects. Harmine is at least partially accountable for the antinociceptive properties of AYA.


Subject(s)
Banisteriopsis , Chronic Pain , Neuralgia , Mice , Animals , Chronic Pain/drug therapy , Hyperalgesia/drug therapy , Hyperalgesia/chemically induced , Harmine/adverse effects , Analgesics/adverse effects , Neuralgia/drug therapy , Disease Models, Animal
2.
Clin Exp Hypertens ; 46(1): 2297642, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38147409

ABSTRACT

Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling caused by the excessive proliferation and survival of pulmonary artery smooth muscle cells (PASMCs). Dual-specificity tyrosine regulated kinase 1A (DYRK1A) is a pleiotropic kinase involved in the regulation of multiple biological functions, including cell proliferation and survival. However, the role and underlying mechanisms of DYRK1A in PAH pathogenesis remain unclear. We found that DYRK1A was upregulated in PASMCs in response to hypoxia, both in vivo and in vitro. Inhibition of DYRK1A by harmine significantly attenuated hypoxia-induced pulmonary hypertension and pulmonary artery remodeling. Mechanistically, we found that DYRK1A promoted pulmonary arterial remodeling by enhancing the proliferation and survival of PASMCs through activating the STAT3/Pim-1/NFAT pathway, because STAT3 gain-of-function via adeno-associated virus serotype 2 (AAV2) carrying the constitutively active form of STAT3 (STAT3C) nearly abolished the protective effect of harmine on PAH. Collectively, our results reveal a significant role for DYRK1A in pulmonary arterial remodeling and suggest it as a drug target with translational potential for the treatment of PAH.


Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Pulmonary Arterial Hypertension/metabolism , Vascular Remodeling , Harmine/adverse effects , Harmine/metabolism , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/metabolism , Pulmonary Artery , Hypoxia , Myocytes, Smooth Muscle/metabolism , Cell Proliferation , Cells, Cultured , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/pharmacology
3.
J Psychoactive Drugs ; 51(1): 3-11, 2019.
Article in English | MEDLINE | ID: mdl-30582439

ABSTRACT

Ayahuasca is a beverage obtained from decoctions of the liana Banisteriopsis caapi plus the shrub Psychotria viridis. This beverage contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for its visionary effect. The ritualistic use of ayahuasca is becoming a global phenomenon. Most members of ayahuasca churches consume this beverage throughout their life, and many reports have discussed the therapeutic potential of this beverage. Ayahuasca is consumed orally, and the liver, as the major organ for the metabolism and detoxification of xenobiotics absorbed from the alimentary tract, may be susceptible to injury by compounds present in the ayahuasca decoction. In this study, we evaluated biochemical parameters related to hepatic damage in the serum of 22 volunteers who consumed ayahuasca twice a month or more for at least one year. There was no significant alteration in the following parameters: alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, urea, lactate dehydrogenase, alkaline phosphatase, and gamma glutamyl transferase. These findings indicate that chronic ayahuasca consumption in a religious context apparently does not affect hepatic function.


Subject(s)
Banisteriopsis/adverse effects , Liver/drug effects , Plant Extracts/adverse effects , Adult , Aged , Beverages/adverse effects , Ceremonial Behavior , Female , Hallucinogens/adverse effects , Harmine/adverse effects , Harmine/analogs & derivatives , Humans , Liver Function Tests/methods , Male , Middle Aged , N,N-Dimethyltryptamine/adverse effects , Substance-Related Disorders/physiopathology , Young Adult
4.
PLoS One ; 13(10): e0204828, 2018.
Article in English | MEDLINE | ID: mdl-30281642

ABSTRACT

Naturally occurring entomopathogenic fungi such as Conidiobolus coronatus are important regulatory factors of insect populations. GC-MS analysis of fungal cell-free filtrates showed that C. coronatus synthesizes two ß- carboline alkaloids: harman and norharman. Significantly higher levels of both alkaloids are produced by C. coronatus in minimal postincubation medium than in rich medium. The beta-carboline alkaloids may have an effect on the nervous system of insects and their behavior. Harman and norharman were applied to Galleria mellonella larvae (a parasite of honeybees) either topically or mixed with food. Larvae received alkaloids in three concentrations: 750, 1000 or 1250 ppm. The effect on the survival and further development of larvae was examined. Both harman and norharman delayed pupation and adult eclosion, and inhibit total monoamine oxidase activity. In addition, they increased the serotonin concentration and decreased the monoamine oxidase A level in the heads of the moths. It is likely that the alkaloids were metabolized by the insects, as their effect wore off 24 hours after topical application. This is the first study to show that C. coronatus produces alkaloids. Its aim was to identify the actions of ß-carboline alkaloids on insect development and serotonin-regulating enzymes. Knowledge of the potential role of harman and norharman in the process of fungal infection might lead to the development of more effective and environmentally-friendly means of controlling insect pests.


Subject(s)
Carbolines/adverse effects , Conidiobolus/growth & development , Harmine/analogs & derivatives , Monoamine Oxidase/metabolism , Moths/growth & development , Animals , Carbolines/isolation & purification , Conidiobolus/chemistry , Gas Chromatography-Mass Spectrometry , Gene Expression Regulation, Developmental , Harmine/adverse effects , Harmine/isolation & purification , Insect Proteins/metabolism , Larva/enzymology , Larva/growth & development , Moths/enzymology , Moths/microbiology , Serotonin/metabolism , Solid Phase Extraction
5.
Physiol Behav ; 194: 239-245, 2018 10 01.
Article in English | MEDLINE | ID: mdl-29885919

ABSTRACT

Chronic stress induces hippocampal-dependent memory deficits, which can be counterbalanced with prolonged exercise. On the other hand, the ß-carboline alkaloid harmane exerts potential in therapies for Alzheimer's and depression diseases and modulating neuronal responses to stress. The present study investigated the effect of chronic treatment of harmane alone or during treadmill running on spatial memory deficit in restraint-stressed mice. To examine spatial memory, adult male NMRI mice were subjected to the Y-maze. Intraperitoneal administration of harmane (0.6 mg/kg, once/ 48 h for 25 days) decreased the percentage of time in the novel arm and the number of novel arm visits, indicating a spatial memory deficit. A 9-day restraint stress (3 h/day) also produced spatial learning impairment. However, a 4-week regime of treadmill running (10 m/min for 30 min/day, 5 days/week) aggravated the stress impairing effect on spatial learning of 3-day stressed mice compared to exercise/non-stressed mice. Moreover, harmane (0.3 mg/kg) associated with exercise increased the number of novel arm visits in 9-day stressed mice compared to harmane/exercise/non-stressed or 9-day stressed group. It should be noted that none of these factors alone or in combination with each other had no effect on locomotor activity. Taken together, these data suggest that there is no interaction between harmane and exercise on spatial memory in stress condition.


Subject(s)
Harmine/analogs & derivatives , Memory Disorders/etiology , Neurotoxins/adverse effects , Running/psychology , Stress, Psychological/complications , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Harmine/adverse effects , Learning Disabilities/etiology , Learning Disabilities/physiopathology , Male , Maze Learning/drug effects , Maze Learning/physiology , Memory Disorders/physiopathology , Mice , Recognition, Psychology/drug effects , Recognition, Psychology/physiology , Restraint, Physical , Running/physiology , Spatial Memory/drug effects , Spatial Memory/physiology , Stress, Psychological/physiopathology , Time Factors
6.
Org Biomol Chem ; 16(12): 2170-2184, 2018 03 28.
Article in English | MEDLINE | ID: mdl-29528081

ABSTRACT

Photodynamic therapy (PDT) is an emerging clinical treatment currently being used against a wide range of both cancerous and noncancerous diseases. The search for new active photosensitizers as well as the development of novel selective delivery systems are the major challenges faced in the application of PDT. We investigated herein three chloroharmine derivatives (6-, 8- and 6,8-dichloroharmines) with quite promising intrinsic photochemical tunable properties and their ability to photoinduce DNA damage in order to elucidate the underlying photochemical mechanisms. Data revealed that the three compounds are quite efficient photosensitizers. The overall extent of photo-oxidative DNA damage induced by both 8-chloro-substituted ß-carbolines is higher than that induced by 6-chloro-harmine. The predominant type of lesion generated also depends on the position of the chlorine atom in the ß-carboline ring. Both 8-chloro-substituted ß-carbolines mostly oxidize purines via type I mechanism, whereas 6-chloro-harmine mainly behaves as a "clean" artificial photonuclease inducing single-strand breaks and site of base loss via proton transfer and concerted (HO--mediated) hydrolytic attack. The latter finding represents an exception to the general photosensitizing reactions and, to the best of our knowledge, this is the first time that this process is well documented. The controlled and selective production of different oxygen-independent lesions could be fine-tuned by simply changing the substituent groups in the ß-carboline ring. This could be a promising tool for the design and development of novel photo-therapeutic agents aimed to tackle hypoxic conditions shown in certain types of tumours.


Subject(s)
DNA Damage/drug effects , Harmine/adverse effects , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Antineoplastic Agents/pharmacology , Chlorine , DNA Breaks, Single-Stranded , Harmine/analogs & derivatives , Hydrolysis , Isomerism , Oxidation-Reduction
7.
BMC Complement Altern Med ; 17(1): 517, 2017 Dec 02.
Article in English | MEDLINE | ID: mdl-29197358

ABSTRACT

BACKGROUND: Compound Muniziqi granule (MNZQ) is a multi-component herbal preparation and a popular traditional Uighur medicine used in China for treating endocrine disorder-induced acne, chloasma, dysmenorrhea, menopausal syndrome, and melanoma. Harmine presented in MNZQ has been confirmed potential anticancer effect on the B16 cells among others. The purpose of this study is to explore the inhibitory effects of MNZQ against B16 cells and mechanism of autophagy and apoptosis induced by harmine in B16 cells. METHODS: The cell viability was calculated by CCK8 assay. The in vitro tyrosinase activity was determined by spectrophotometry. The harmine-induced autophagy was demonstrated by electron microscopy and MDC staining. Flow cytometry was used to measure cell death and cell cycle distribution. All proteins expression was assessed by western blot. RESULTS: MNZQ and some herb extracts contained in preparation displayed inhibitory effects on B16 cells but without inhibition on mushroom tyrosinase compared with kojic acid. The formation of autophagosome was markedly induced by harmine with the accretion of LC3-II and the degeneration of p62 in B16 cells, which indicated that harmine was an autophagy inducer. Cell death and sub-G2 population suggested that harmine could induce cell death. Particularly, 3-MA, an autophagy inhibitor, was discovered to prevent harmine-induced decrease of the cell viability and cell cycle arrest on G2 phase, indicating that autophagy was vital to the cell death. In addition, the results indicated that harmine could inhibit the phosphorylation of Akt and mTOR, which might mediate autophagy. CONCLUSION: Harmine could induce autophagy and apoptosis by inhibiting Akt/mTOR pathway in B16 cells. Harmine might be a promising therapeutic agent for treatment of melanoma in MNZQ.


Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Drugs, Chinese Herbal/pharmacology , TOR Serine-Threonine Kinases/metabolism , Animals , Cell Line, Tumor , Cell Survival/drug effects , Harmine/adverse effects , Melanoma, Experimental , Mice , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects
8.
Physiol Behav ; 138: 260-5, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25250831

ABSTRACT

Harmine is a naturally occurring monoamine oxidase inhibitor that has recently been shown to selectively inhibit the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (DYRK1A). We investigated the cognitive effects of 1mg (low) Harmine and 5mg (high) Harmine using the delayed-match-to-sample (DMS) asymmetrical 3-choice water maze task to evaluate spatial working and recent memory, and the Morris water maze task (MM) to test spatial reference memory. Animals were also tested on the visible platform task, a water-escape task with the same motor, motivational, and reinforcement components as the other tasks used to evaluate cognition, but differing in its greater simplicity and that the platform was visible above the surface of the water. A subset of the Harmine-high treated animals showed clear motor impairments on all behavioral tasks, and the visible platform task confirmed a lack of competence to perform the procedural components of water maze testing. After excluding animals from the high dose group that could not perform the procedural components of a swim task, it was revealed that both high- and low-dose treatment with Harmine enhanced performance on the latter portion of DMS testing, but had no effect on MM performance. Thus, this study demonstrates the importance of confirming motor and visual competence when studying animal cognition, and verifies the one-day visible platform task as a reliable measure of ability to perform the procedural components necessary for completion of a swim task.


Subject(s)
Harmine/pharmacology , Maze Learning/drug effects , Memory, Short-Term/drug effects , Nootropic Agents/pharmacology , Aging , Animals , Cognition/drug effects , Dose-Response Relationship, Drug , Dyskinesia, Drug-Induced , Harmine/adverse effects , Male , Maze Learning/physiology , Memory, Short-Term/physiology , Motor Activity/drug effects , Neuropsychological Tests , Nootropic Agents/adverse effects , Random Allocation , Rats, Inbred F344 , Spatial Memory/drug effects
9.
Neurotoxicology ; 34: 264-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22981972

ABSTRACT

BACKGROUND: Environmental correlates for essential tremor (ET) are largely unexplored. The search for such environmental factors has involved the study of a number of neurotoxins. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing toxin. In two prior case-control studies in New York, we demonstrated that blood harmane concentration was elevated in ET patients vs. controls, and especially in familial ET cases. These findings, however, have been derived from a study of cases ascertained through a single tertiary referral center in New York. OBJECTIVE: Our objective was to determine whether blood harmane concentrations are elevated in familial and sporadic ET cases, ascertained from central Spain, compared to controls without ET. METHODS: Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method. RESULTS: The median harmane concentrations were: 2.09 g(-10)/ml (138 controls), 2.41 g(-10)/ml (68 sporadic ET), and 2.90 g(-10)/ml (62 familial ET). In an unadjusted logistic regression analysis, log blood harmane concentration was not significantly associated with diagnosis (familial ET vs. control): odds ratio=1.56, p=0.26. In a logistic regression analysis that adjusted for evaluation start time, which was an important confounding variable, the odds ratio increased to 2.35, p=0.049. CONCLUSIONS: Blood harmane levels were slightly elevated in a group of familial ET cases compared to a group of controls in Spain. These data seem to further extend our observations from New York to a second cohort of ET cases in Spain. This neurotoxin continues to be a source of interest for future confirmatory research.


Subject(s)
Environmental Pollutants/blood , Essential Tremor/blood , Harmine/analogs & derivatives , Neurotoxicity Syndromes/blood , Aged , Aged, 80 and over , Analysis of Variance , Case-Control Studies , Chi-Square Distribution , Chromatography, High Pressure Liquid , Environmental Pollutants/adverse effects , Essential Tremor/chemically induced , Essential Tremor/epidemiology , Essential Tremor/physiopathology , Female , Harmine/adverse effects , Harmine/blood , Humans , Logistic Models , Longitudinal Studies , Male , Middle Aged , Neurotoxicity Syndromes/epidemiology , Neurotoxicity Syndromes/physiopathology , Odds Ratio , Risk Assessment , Risk Factors , Spain/epidemiology , Up-Regulation
10.
Prog Neuropsychopharmacol Biol Psychiatry ; 39(2): 263-72, 2012 Dec 03.
Article in English | MEDLINE | ID: mdl-22691716

ABSTRACT

Ayahuasca is a hallucinogenic botanical mixture originating in the Amazon area where it is used ritually, but is now being taken globally. The 2 main constituents of ayahuasca are N,N-dimethyltryptamine (DMT), a hallucinogen, and harmine, a monoamine oxidase inhibitor (MAOI) which attenuates the breakdown of DMT, which would otherwise be broken down very quickly after oral consumption. Recent developments in ayahuasca use include the sale of these compounds on the internet and the substitution of related botanical (anahuasca) or synthetic (pharmahuasca) compounds to achieve the same desired hallucinogenic effects. One intriguing result of ayahuasca use appears to be improved mental health and a reduction in recidivism to alternate (alcohol, cocaine) drug use. In this review we discuss the pharmacology of ayahuasca, with a focus on harmine, and suggest pharmacological mechanisms for the putative reduction in recidivism to alcohol and cocaine misuse. These pharmacological mechanisms include MAOI, effects at 5-HT(2A) and imidazoline receptors and inhibition of dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) and the dopamine transporter. We also speculate on the therapeutic potential of harmine in other CNS conditions.


Subject(s)
Alcoholism/prevention & control , Cocaine-Related Disorders/prevention & control , Harmine/pharmacology , Harmine/therapeutic use , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/therapeutic use , Alcoholism/drug therapy , Animals , Banisteriopsis/chemistry , Cocaine-Related Disorders/drug therapy , Harmine/adverse effects , Harmine/pharmacokinetics , Humans , Monoamine Oxidase Inhibitors/adverse effects , Monoamine Oxidase Inhibitors/pharmacokinetics , N,N-Dimethyltryptamine/pharmacology , Secondary Prevention
11.
Neurotoxicology ; 29(2): 294-300, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18242711

ABSTRACT

Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high-performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3+/-15.5 vs. 65.5+/-14.2 years, p=0.94). Mean log blood harmane concentration was approximately 50% higher in cases than controls (0.50+/-0.54g(-10)/ml vs. 0.35+/-0.62g(-10)/ml, p=0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (OR(adjusted) 1.56, 95% CI 1.01-2.42, p=0.04), and odds of ET was 1.90 (95% CI 1.07-3.39, p=0.029) in the highest versus lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53+/-0.57g(-10)/ml), intermediate in cases with sporadic ET (0.43+/-0.45g(-10)/ml) and lowest in controls (0.35+/-0.62g(-10)/ml) (test for trend, p=0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors.


Subject(s)
Environmental Pollutants/blood , Essential Tremor/blood , Harmine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Case-Control Studies , Chromatography, High Pressure Liquid , Environmental Pollutants/adverse effects , Essential Tremor/chemically induced , Essential Tremor/genetics , Female , Genetic Predisposition to Disease , Harmine/adverse effects , Harmine/blood , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Risk Assessment , Risk Factors , Up-Regulation
12.
Neurology ; 69(6): 515-20, 2007 Aug 07.
Article in English | MEDLINE | ID: mdl-17679670

ABSTRACT

BACKGROUND: On proton magnetic resonance spectroscopic imaging ((1)H MRSI), there is a decrease in cerebellar N-acetylaspartate/total creatine (NAA/tCr) in essential tremor (ET), signifying cerebellar neuronal dysfunction or degeneration. Harmane, which is present in the human diet, is a potent tremor-producing neurotoxin. Blood harmane concentrations seem to be elevated in ET. OBJECTIVES: To assess in patients with ET whether blood harmane concentration is correlated with cerebellar NAA/tCR, a neuroimaging measure of neuronal dysfunction or degeneration. METHODS: Twelve patients with ET underwent (1)H MRSI. The major neuroanatomic structure of interest was the cerebellar cortex. Secondary regions were the central cerebellar white matter, cerebellar vermis, thalamus, and basal ganglia. Blood concentrations of harmane and another neurotoxin, lead, were also assessed. RESULTS: Mean +/- SD cerebellar NAA/tCR was 1.52 +/- 0.41. In a linear regression model that adjusted for age and gender, log blood harmane concentration was a predictor of cerebellar NAA/tCR (beta = -0.41, p = 0.009); every 1 g(-10)/mL unit increase in log blood harmane concentration was associated with a 0.41 unit decrease in cerebellar NAA/tCR. The association between blood harmane concentration and brain NAA/tCR only occurred in the cerebellar cortex; it was not observed in secondary brain regions of interest. Furthermore, the association was specific to harmane and not another neurotoxin, lead. CONCLUSION: This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.


Subject(s)
Cerebellar Cortex/metabolism , Essential Tremor/blood , Harmine/analogs & derivatives , Neurotoxins/blood , Aspartic Acid/analogs & derivatives , Aspartic Acid/analysis , Basal Ganglia/chemistry , Cerebellar Cortex/chemistry , Cerebellum/chemistry , Creatine/analysis , Female , Harmine/adverse effects , Harmine/blood , Humans , Lead/blood , Male , Nuclear Magnetic Resonance, Biomolecular , Pilot Projects , Single-Blind Method , Thalamus/chemistry , Videotape Recording
13.
Psychopharmacology (Berl) ; 173(1-2): 79-87, 2004 Apr.
Article in English | MEDLINE | ID: mdl-14712339

ABSTRACT

RATIONALE: During binocular rivalry, two incompatible images are presented to each eye and these monocular stimuli compete for perceptual dominance, with one pattern temporarily suppressed from awareness. One variant of stimulus presentation in binocular rivalry experiments is dichoptic stimulus alternation (DSA), when stimuli are applied to the eyes in rapid reversals. There is preliminary report that in contrast with healthy controls, schizophrenic patients can maintain binocular rivalry even at very high DSA rates. OBJECTIVE: The study was undertaken to investigate whether binocular rivalry survives high rates of DSA induced by the South American hallucinogenic beverage ayahuasca. METHODS: Ten individuals who were participating in ayahuasca ceremonials were requested to volunteer for binocular rivalry tests (DSA=0, 3.75, 7.5, 15 and 30 Hz) without and after drinking the brew. RESULTS: Ingestion of ayahuasca increased mean dominance periods both in standard binocular rivalry conditions (no DSA) and tests with DSA. At higher DSA rates (15 and 30 Hz) the total length of dominance periods was longer on the brew. CONCLUSION: It is discussed that ayahuasca-induced survival of binocular rivalry at high DSA rates may be related to slow visual processing and increased mean dominance periods may result from hallucinogen-induced alteration of gamma oscillations in the visual pathways.


Subject(s)
Banisteriopsis/chemistry , Hallucinogens/adverse effects , Vision Disparity/drug effects , Vision, Binocular/drug effects , Visual Perception/drug effects , Adult , Aged , Female , Hallucinogens/pharmacology , Harmine/adverse effects , Harmine/pharmacology , Humans , Male , Middle Aged , Photic Stimulation/methods , Plant Extracts/pharmacology , Psychomotor Performance/drug effects , Vision Disparity/physiology , Vision, Binocular/physiology , Visual Perception/physiology
14.
J Psychoactive Drugs ; 35(3): 367-74, 2003.
Article in English | MEDLINE | ID: mdl-14621134

ABSTRACT

An early theoretical analysis supposed changes in hemispheric integration as the basis of altered state of consciousness induced by psychoactive drugs. Brain imaging studies revealed right cortical activation after administration of hallucinogens. Recent studies on binocular rivalry suggest that interhemispheric switching is the neural substrate of the perceptual oscillations observed during dichoptic stimulus presentation. The current study tested perceptual alternation in ceremonial participants, who ingested the South American hallucinogenic beverage ayahuasca, to examine the claim that there might be changes in interhemispheric function under the influence of hallucinogens. Ingestion of ayahuasca resulted in a decrease of rivalry alternation rates, increased length of one percept and there was evidence of phenomenal fusion. The findings are in line with results of brain activation studies and support the concept of interhemispheric fusion in altered states of consciousness.


Subject(s)
Banisteriopsis/chemistry , Dominance, Cerebral/drug effects , Dominance, Ocular/drug effects , Hallucinogens/adverse effects , Vision, Binocular/drug effects , Visual Perception/drug effects , Adult , Aged , Beverages , Dominance, Cerebral/physiology , Dominance, Ocular/physiology , Female , Hallucinogens/pharmacology , Harmine/adverse effects , Harmine/pharmacology , Humans , Male , Middle Aged , Plant Preparations/adverse effects , Plant Preparations/pharmacology , Vision, Binocular/physiology , Visual Perception/physiology
15.
J Toxicol Clin Toxicol ; 38(1): 63-6, 2000.
Article in English | MEDLINE | ID: mdl-10696928

ABSTRACT

BACKGROUND: Herbal medicines may have significant adverse effects which are not suspected or recognized. CASE REPORT: A 34-year-old female developed severe nausea, vomiting, drowsiness, prolonged QTc, and episodes of nonsustained ventricular tachycardia following self-administration of a herbal remedy, Passiflora incarnata L., at therapeutic doses. The possible association of symptoms with passiflora was not recognized for several days. She required hospital admission for cardiac monitoring and intravenous fluid therapy. CONCLUSIONS: Passiflora incarnata was associated with significant adverse effects in this patient. It is important to ask specifically about the use of herbal medicines in patients with undiagnosed illnesses.


Subject(s)
Plants, Medicinal/adverse effects , Adult , Electrocardiography/drug effects , Female , Harmine/adverse effects , Harmine/analogs & derivatives , Humans , Nausea/chemically induced , Tachycardia, Ventricular/chemically induced , Vomiting/chemically induced
17.
Alcohol Clin Exp Res ; 12(5): 679-82, 1988 Oct.
Article in English | MEDLINE | ID: mdl-3067615

ABSTRACT

Harman, a beta-carboline compound, was identified and quantitated in beer and wine samples using a combination of high performance liquid chromatography with fluorescence detection and gas chromatography-negative chemical ionization mass spectrometry. The concentration of harman in beer (7.3-140.0 ng/ml) was greater than in wine (0.8-10.5 ng/ml) and was not related to alcohol content. The pharmacological and toxicological implications of harman in alcoholic beverages are discussed.


Subject(s)
Alcoholic Beverages/analysis , Alkaloids/analysis , Harmine/analysis , Alcoholic Beverages/adverse effects , Beer/analysis , Chromatography, High Pressure Liquid , Harmine/adverse effects , Harmine/analogs & derivatives , Humans , Wine/analysis
18.
J Pharmacobiodyn ; 4(7): 520-7, 1981 Jul.
Article in English | MEDLINE | ID: mdl-6975366

ABSTRACT

Harmine, a hallucinogen with potent monoamine oxidase inhibitory properties, induced abnormal behavior, including tremor, scratching, head twitch and cage biting, in the mouse. A dose-dependent tremor was produced by all routes of administration of harmine. Although oxotremorine tremor was markedly suppressed by atropine, harmine tremor was unaffected by cholinergic drugs, remarkably inhibited by dopaminergic drugs, antidepressants and diazepam, mildly diminished by p-chlorophenylalanine, markedly augmented by 5-hydroxytryptophan and mildly increased by alpha-methyl-p-tyrosine. These findings suggest that a catecholaminergic (particularly dopaminergic) and serotonergic system imbalance plays an important role in the manifestation of harmine tremor. In view of these characteristics, harmine tremor may be useful as an effective experimental model for the evaluation of antiparkinsonism drugs, along with oxotremorine tremor because of the different mechanism of occurrence. In addition, harmine tremor appears to be useful in characterizing the properties of antidepressant drugs.


Subject(s)
Alkaloids/adverse effects , Behavior, Animal/drug effects , Harmine/adverse effects , Tremor/chemically induced , 5-Hydroxytryptophan/pharmacology , Animals , Antidepressive Agents/pharmacology , Diazepam/pharmacology , Disease Models, Animal , Dopamine/pharmacology , Dose-Response Relationship, Drug , Harmine/antagonists & inhibitors , Harmine/pharmacology , Male , Mice , Oxotremorine/pharmacology
19.
Agents Actions ; 5(1): 57-61, 1975 Feb.
Article in English | MEDLINE | ID: mdl-1180178

ABSTRACT

Injection of the tremorigenic alkaloid harmine into lymphostatic encephalopathic rats leads to a longer duration of tremor and higher brain concentrations than in sham-operated controls. In lymphostatic encephalopathic as well as in normal rats different antiphlogistics shorten the tremor duration and decrease harmine concentration in brain. The antiphlogistics do not influence the plasma concentration of harmine, its protein binding and its tremorend concentration in brain. The effect of antiphlogistics in lymphostatic encephalopathic rats is considered as a consequence of the reduced blood-brain barrier permeability. Obviously in sick animals the blood-brain barrier permeability for harmine is not increased; the prolonged harmine tremor and the increased alkaloid concentration in the brain are consequences of the impaired cerebral lymphatic drainage only.


Subject(s)
Alkaloids/pharmacology , Anti-Inflammatory Agents/pharmacology , Blood-Brain Barrier/drug effects , Brain Diseases/physiopathology , Harmine/pharmacology , Animals , Brain Chemistry/drug effects , Harmine/adverse effects , Harmine/analysis , Harmine/blood , Male , Rats , Time Factors , Tremor/chemically induced
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