QEEG Studies of the Effects of Natural and Synthetic DMT
The objective of this exploratory research was to examine the neurophysiological correlates of DMT action on the human brain using QEEG brain mapping techniques. Quantitative EEG (QEEG) is an established reliable electrophysiological technique to measure electrical brain function. EEG recorded waveforms are oscillations at different frequencies measured at the scalp that reflect synchronized neural network information processing in different brain areas responsible for cognition, affect, and behavior. Moreover, internal subjective states exhibit distinct brainwave correlates.
An earlier QEEG study examined the acute effects of the entheogenic plant Salvia divinorum (Acosta-Urquidi, J. Neurotherapy, 12(1), 57-58, 2008), delivered by smoked inhalation of Salvia 10x extract. The rapid onset, short acting (10-20 min.) and reversible nature of the effects demonstrated the feasibility of conducting such EEG studies. This experience was applied to the present study using the psychoactive DMT . Two sources of smoked DMT were tested: high purity synthetic 5-MeO- DMT and N,N DMT from a natural extract of Mimosa hostilis root bark. The rapid onset and time course of effects were similar to the Salvia studies. Dosage was adjusted to elicit an effective “trip”. Healthy adult men and women volunteers (N=10; age: 33-55), were studied with QEEG, employing Mitsar amplifier, 10-20 system electrocap, 19 channels referential linked ears montage, 0.5-40 Hz bandwidth.
Artifacted raw data was analysed with Neuroguide software. A 10 min. baseline control recording (resting eyes closed) was first obtained, followed by the smoked DMT condition, lasting 10-15 min. A recovery post-DMT EEG was also recorded at 10-20 min., when subjects reported a full recovery to ordinary consciousness. The DMT-evoked profound alterations in consciousness correlated with EEG changes revealed in the topographic brain maps and FFT power-frequency spectra of the subjects tested. Variable significant effects on select frequency bands were encountered: robust increases (up to 250% ) and decreases (31-66%, 4 subjects ) in Absolute Alpha power; shifts in peak frequency from Alpha to Theta (in 5 subjects); coherence and phase metrics were also changed. In some cases, partial to full reversibility of the effects was measured.
The significance of these preliminary findings is discussed with reference to DMT receptor pharmacology mechanisms (Fontanilla, D et al., Science. 2009,13; 323(5916): 934–937; Jacob, MS and Presti, DE, Medical Hypotheses 2005, 64: 930–937) and the EEG/Ayahuasca studies reported.
Dr. Juan Acosta-Urquidi entered the field of QEEG (quantitative electroencephalography) in 1996. Initially, he worked with QEEG to test photic and auditory driving responses to mind machines. He then joined an NIH-funded project in alternative medici e at the University of Washington Medical Center to study pulsed magnetotherapy treatment on neurologic patients suffering MS. While still there, a chance discovery lead him to pursue research with Energy Healers, at a time when he was initiated as a Reiki Master. Using an electrocrystal detector device he recorded electromagnetic signals emanating from Energy Healers during the state of “sending”, or “channeling” energy. He extended this research by simultaneously measuring EEG in a subset of the healers sample, documenting the shifting brainwave patterns as the healers transit through different states of consciousness during the energy healing state. These topographic brain maps, with the recent addition of HRV (heart rate variability) measurements, have been yielding rich data on the heart-brain exchange, charting new ground in the research interface of Science, Healing and Spirituality. His achievements include; Ph.D, Cellular Neurophysiology, 1980, University of Toronto; A.B. Biophysics, 1971, University of California, Berkeley; MSc. Neurobiology, 1974, McGill University, Montreal, CAN. Member International Society for the Study of Subtle Energy and Energy Medicine (ISSSEEM),1996- present; Biofeedback Society of Washington, 2002; Association of Applied Psychophysiology and Biofeedback (AAPB), 2002, 2006-08, 09; International Society for Neurofeedback and Research (ISNR), 2005-present. Invited presenter at EGA 2011.
The Phenomenology of Salvia Divinorum Inebriation
Salvinorin A (SA), a potent and selective nonnitrogenous kappa opioid receptor (KOR) agonist, is an increasingly popular recreational drug. There is increasing interest in the effects of SA, but there is a lack of scientific literature regarding the phenomenology of SA inebriation, the similarities and differences with other nonordinary states of consciousness, and the abuse potential of SA. It is contentious whether or not SA can be called a psychedelic drug. Our objective was to address this lack by systematically recording and analyzing the acute subjective effects of SA under controlled conditions.
In a double-blind, randomized, crossover study 30 healthy adults self-administered either a non-psychoactive dose of 100 mcg SA or a psychoactive dose of 1017 mcg SA in counterbalanced order in a controlled setting two weeks apart. Real-time and retrospective interviews of participants describing their experiences were recorded and transcribed. Transcripts were systematically analyzed by three raters using thematic analysis to elicit commonly-reported themes.
SA inebriation consisted of subjectively-rated unique experiences, including visual-tactile synesthesia, perceived reality distortion, and somaesthetic changes, which were incomparable to any other altered states of consciousness directly experienced by the participants. However, there was also some overlap with serotonergic psychedelics, including kaleidoscopic imagery and perceived contact with nonhuman entities.
Peter H Addy, PhD is currently a postdoctoral associate in psychiatry at Yale School of Medicine and a psychology resident at the Substance Abuse Treatment Unit, CT Mental Health Center. His position at Yale involves working with the Schizophrenia and Neuropharmacology Research Group understanding the acute effects of cannabis, Salvia divinorum, ketamine, and other psychoactive substances. His clinical work at SATU is providing individual outpatient therapy to adults with substance use issues and facilitating a weekly mindfulness-based relapse prevention group. Peter’s dissertation was a study of the acute behavioral and subjective effects of Salvia divinorum, a plant used in shamanic practices in central Mexico.
Characterization of Challenging Experiences (i.e., Bad Trips) After Ingesting Psilocybin
Aims: High-dose psilocybin sessions in supportive contexts have recently been reported to have sustained positive effects on attitudes, mood, and behavior. However, difficult experiences (i.e., ‘bad trips,’ which may include fear, anxiety, or paranoia) have been observed in some cases. The present analysis of high dose psilocybin sessions characterizes the incidence and predictors of having a bad trip and the correlation between bad trips and mystical experiences.
Methods: This analysis characterized bad trips from two previous studies (N= 54 participants at 30 mg/70kg psilocybin). Incidence of participant-rated fear, anxiety, and paranoia were examined using individual items (see below). Correlations were examined between participant post-session ratings of bad trips [the AIA (dread of ego dissolution) subscale of the APZ (an altered consciousness measure) and the sum of 10 ‘bad trip’ items from the States of Consciousness Questionnaire (SOCQ) and Hallucinogen Rating Scale (HRS)] with demographics, personality measures, and a post-session measure of mystical experience.
Results: Participants rated strong or extreme “fear” (24%, 13/54) and anxiety (“trapped and helpless”) (20%, 11/54); 17% (9/54) reported paranoia (“people… plotting against”) at some point during the session. Younger participants had higher bad trip scores (AIA, r = -.33, p <.05; SOCQ/HRS, r = -.27, p <.05). AIA scores were significantly correlated with mystical experience scores (r = .36, p<.01).
Conclusions: Subjective-effects measures indicated substantial incidence of bad trip effects during high dose psilocybin sessions. Being younger seemed to increase risk for these experiences. However, such experiences were positively correlated with having a mystical experience. Further results from these experimental data and a survey of the general population will be reported at the conference.
Support: NIDA grants R01DA03889 & T32DA007209, The Council on Spiritual Practices, The Heffter Research Institute
I’m postdoctoral fellow at Johns Hopkins University School of Medicine in Baltimore, MD. I am involved with a research team lead by Roland Griffiths, Ph.D. that investigates the subjective and behavioral effects of hallucinogens as well as their use in the treatment of anxiety among cancer patients and their effects in aiding meditation. Prior to this I attended graduate school at the University of Vermont in Burlington, VT where I was involved in smoking cessation research investigating the use of financial incentives to promote abstinence. In my spare time I enjoy hanging out with my wife and our long-haired chihuahua, appreciating the outdoors and nature anyway I can, watching movies, and reading automotive enthusiast publications.
Indolethylamine N-methyltransferase Expression in Primate Nervous Tissue
N,N-dimethyltryptamine (DMT) is a naturally-occurring indole hallucinogen found in plants, animals, and humans, but its biological role has not been fully characterized. DMT has been proposed to act as a neurotransmitter in humans and to be involved in psychosis, dreaming, near-death experiences, and spiritual exaltation. DMT is biosynthesized from tryptamine through the actions of the enzyme indolethylamine N-methyltransferase (INMT). Using S-adenosyl methionine as the methyl donor, INMT catalyzes the addition of methyl groups to tryptamine and analogous indole alkylamines.
Human INMT was cloned and sequenced in 1999. Assessment of human INMT expression by Northern blot analysis in 35 tissues revealed widespread INMT mRNA distribution with high levels in thyroid, adrenal gland, and lung. However, in the central nervous system, INMT mRNA was detected only in the spinal cord, but not in whole brain or in seven brain subregions. This observation suggested that INMT may not be involved in DMT biosynthesis in the brain and calls into question the role, if any, of endogenous DMT in producing exceptional mental states. To explore the possibility that INMT is expressed in nervous tissue but that in some situations, INMT mRNA is not detectable by Northern analysis (e.g. the INMT gene is inducible, INMT expression is limited to specific brain nuclei, or INMT mRNA in brain is short-lived), we probed three primate nervous system tissues with antibodies to INMT itself. The antibodies were generated against the C-terminus of human INMT during the original cloning of the human INMT gene. Rhesus macaque spinal cord, pineal gland, and retina were probed with rabbit polyclonal antibodies to human INMT and with mouse antibodies to synaptophysin and synaptotagmin. Nuclear DNA was visualized with 4',6-diamidino-2-phenylindole (DAPI). Binding of primary antibodies to the tissues was visualized with fluorescent goat anti-rabbit and goat anti-mouse secondary antibodies. All three of the nervous tissues tested were positive for INMT immunoreactivity. In agreement with earlier Northern studies in human tissue, INMT immunoreactivity was detected in spinal cord where it was localized in ventral horn motoneurons. In the pineal gland, the INMT signal was robust and punctuate but did not colocalize with synaptophysin, synaptotagmin, or DAPI. Strong INMT immunoreactivity was detected in retinal ganglion neurons and at synapses in the inner and outer plexiform layers. We conclude that INMT protein is expressed in some primate central nervous system tissues, but whether INMT expression is associated with the biosynthesis of DMT in neurons remains to be investigated.
Dr. Nicholas Cozzi is a scientist and educator at the University of Wisconsin-Madison School of Medicine and Public Health. He holds a Ph.D. in Pharmacology and a B.S. in Pharmacology and Toxicology, both from the UW-Madison School of Pharmacy.
Dr. Cozzi's research involves the design, chemical synthesis, and pharmacological examination of drugs with central nervous system activity. Compounds of special interest include those with psychedelic, antidepressant, or psychostimulant effects. He is interested in how these substances act in the brain to produce changes in mood, cognition, and other effects including spiritual or mystical experiences. He is internationally recognized for his contributions to neuropharmacology.
Dr. Cozzi teaches pharmacology for students in the UW School of Medicine and Public Health, the UW School of Pharmacy, and the UW School of Veterinary Medicine, and he is a regular guest lecturer at other academic institutions. He has won several teaching awards and is involved in shaping medical education policy at the UW. Outside the University, Dr. Cozzi consults for legal, pharmaceutical, and government clients.
Pluripotent Stem Cells as Tools for Studying the Effects of Psychedelic Substances in Human Neurons
Human induced pluripotent stem (iPS) cells emerged as a new experimental model to study cellular and molecular mechanisms of neuroactive compounds with exclusive advantages such as the generation of live human neurons in vitro. We have previously shown that cannabinoid signaling is functionally implicated in the survival of pluripotent stem cells (Nones et al, 2010). By using a high content screening (HCS) system, here we examined the effect of the cannabinoid agonist WIN55212-2 upon the generation of reactive oxidative species (ROS) in iPS-derived human neurons. We observed a 50% decrease in ROS production after WIN55212-2 treatment, indicating that activation of CB1/CB2 receptors by exogenous cannabinoids reduces both ROS and cell death in human neurons. No increase in proliferation or neural differentiation was observed. By using a similar experimental approach, human neural cells were treated with Ayahuasca (0.1 ng.mL-1 DMT). Increased proliferation of human neural cells was observed after chronic treatment, suggesting that neurogenesis is triggered in human neurons by this psychotropic plant tea, similarly to the observed with classical synthetic antidepressant drugs. Taken together, our results indicate that iPS cells technology combined with HCS will provide an innovative methodology for the identification of unpredicted potential benefits, therapeutic and adverse effects of psychedelic substances in brain cells.
Vanja Dakic earned her Master's in molecular biology at the University of Novi Sad (Serbia) in 2008. Since 2012, she has been a PhD student in National Laboratory of Embryonic Stem Cells, under the supervision of Professor Stevens Rehen (Federal University of Rio de Janeiro, Rio de Janeiro, Brazil). Her PhD project comprises the study of molecular and cellular effects of ayahuasca (DMT) on human neurons derived from induced pluripotent stem (iPS) cells, analyzing its effects by using high content screening tools, dynamic imaging of calcium, PCR, and HPLC.
The Prevalence, Intensity, and Assessment of Craving for MDMA/Ecstasy in Recreational Users
Aims: Evaluate the prevalence, intensity, and correlates of craving for MDMA/ecstasy among recreational users employing a new multi-item self-report questionnaire.
Design and Measurement: Using a web-based data collection procedure, we recruited MDMA/ecstasy users to rate their agreement with eight craving statements immediately before and immediately following 90 seconds of exposure to either ecstasy-related or control stimuli. Each participant then completed questionnaires to measure their motivations for ecstasy consumption, ecstasy refusal self-efficacy, passionate engagement in ecstasy use, substance use history, and demographic information.
Participants: Community sample (n = 240) of individuals who had used ecstasy more than 30 times in their lifetime and at least once every other week over the past six months.
Findings: Fifty percent of participants indicated agreement with at least two (out of eight) statements indicative of craving and 30% agreed with six or more such statements. The questionnaire used to assess craving was internally consistent, unidimensional, and had excellent one-week test-retest reliability. Craving scores varied as a function of both cue exposure (p < .001) and frequency of ecstasy use (p < .01), and were significantly correlated (ps < .01) with ecstasy-related attitudes.
Conclusions: Craving for MDMA/ecstasy may be assessed using this multi-item questionnaire reflecting experiences of desire, intention to use, and anticipated loss of control. Recreational users of MDMA/ecstasy endorse some experiences indicative of craving for this drug, even though only a minority report intense craving, even following explicit cue exposure.
Alan Davis and Harold Rosenberg are with the Psychology Department at Bowling Green State University in Ohio. Their research and clinical interests include drug craving, behavioral self-control skills to reduce one’s drinking and drug use, and acceptability of harm reduction and use reduction. This project was completed as part of Alan’s doctoral work and he continues to be interested in the prevalence and assessment of craving among users of psychedelic substances.
Interdisciplinary Trends in Contemporary Psychedelic Conferences
Psychedelic conferences are a vital component in transforming public perceptions on psychedelics. This poster will present a quantitative and qualitative overview of recent psychedelic conferences, examining both their frequency and varying foci. Discussions on the roles of mind-altering substances in society and their potential influences on knowledge production, health, and creativity are entering the mainstream with increasing frequency, and there is every indication that this trend is still in its earliest phases. Since MAPS inaugurated its 2010 "Psychedelic Science" academic conference in San Jose, there has been a stream of psychedelic conferences taking place internationally with varying strengths and personalities. Within a three-week span between late September and early October 2012 alone, the psychedelic research community gathered at the Psychedemia conference at the University of Pennsylvania; the OPEN Foundation's International Conference on Psychedelic Research in Amsterdam; and the Horizons conference in New York City. Singularly among the factors contributing to this public renaissance is the success of the "new wave" of peer-reviewed scientific research. With mutually reinforcing results coming from institutions like Johns Hopkins, New York University, and the University of California-Los Angeles, the early successes of pilot studies are leading to larger trials and additional phases. This poster will demonstrate a trend towards interdisciplinary academic research and will categorize the broad array of disciplines involved in the contemporary psychedelic research renaissance.
Neşe Devenot is a PhD Candidate in the Program in Comparative Literature and Literary Theory at the University of Pennsylvania, founder of the Psychedemia psychedelics conference, and contributing editor for Reality Sandwich. She received her Bachelor's degree in philosophy and literature from Bard College in Annandale-on-Hudson, NY. Her dissertation relates the contemporary psychedelic renaissance to philosophical debates about the nature of consciousness and the limitations of reductive materialism. She has presented on DMT and hyperspace philosophy at the American Comparative Literature Association annual conference in Vancouver, BC, and on psychedelics in academia at Breaking Convention in Canterbury, UK; the International Drug Policy Reform Conference in California; and Entheogenesis Australis in Victoria, AU.
Ketamine Reduces Negative Affect: Results of a Web-Based Survey
Aims: Ketamine is a widely used dissociative anesthetic and drug of abuse that is also being studied for use an antidepressant. We sought to determine whether non-medical ketamine users with depressive personality traits report a more favorable response to ketamine than do users without such traits.
Methods: Visitors to the erowid.org website between 5/23/11 and 7/29/11 were invited to participate in a survey of non-medical drug use and mood. Participants completed the Depressive Personality Disorder Inventory (DPDI) and retrospectively reported affect (using the Positive and Negative Affect Scales, PANAS) occurring during abstinence and 2 days after drug use.
Results: 18,848 participants completed the survey. 1084 (5.7%) had used ketamine in the last six months and 211 (19.5%) had elevated (≥170) scores in the DPDI. PANAS positive affect was not elevated at 2 days after ketamine use relative to baseline in subjects with depressive personality. However, those without depressive personality (N=873) reported significantly lower positive affect post-ketamine (Δ from baseline=-3.05; 95%CI -3.56 to 2.53) compared to those with depressive traits. Both groups reported lower PANAS negative affect after ketamine use compared to baseline. The magnitude of this change was greater in the depressed group (Δ from baseline=-6.87; -8.04 to -5.70) than in the non-depressed group (Δ from baseline=-2.42; -2.78 to -2.06).
Conclusions: Participants reported lowered negative affect but not elevated positive affect after ketamine. This reduction in negative affect after ketamine was greater in high-DPDI participants, consistent with a possible antidepressant-like effect. Future research is needed to determine whether those with clinical depression report a clinically significant change in mood after non-medical ketamine use. Large samples can be rapidly assembled using Web-based surveys.
Gantt Galloway, PharmD is Executive and Research Director of New Leaf Treatment Center and Senior Scientist at California Pacific Medical Center Research Institute. His principal area of interest is developing improved pharmacologic and behavioral treatments for drug dependencies. Dr. Galloway conducted the first randomized controlled trial of a treatment for methamphetamine. Dr. Galloway’s interests also include the pharmacology, pharmacokinetics, epidemiology, and potential therapeutic uses of psychedelics. In addition the survey work presented at this conference, Dr. Galloway has been involved in studies involving the administration of psychedelics (MDA, MDMA, salvinorin A) to normal volunteers.
Shambhala, the Hyperborean Land and Amanita Muscaria
Shambhala is a uniquely important Buddhist legend. The Buddha is said to have gone to this etheric realm to retrieve the Kalachakra Tantra, source of cosmic and astronomic truths of the universe, as well as the Tibetan Medical system. Its description is quite similar to the Hyperborean Land of Apollo; the most likely location of both is in the Altai Mountains on the Russian Steppes. Both mystical realms are laced with stories of golden fruits and one-eyed, one legged beings which are secret code for Amanita Muscaria mushrooms that turn iridescent gold when dried in the sun. These characteristics are well documented by Gordon Wasson and Carl Ruck in the Greek tale of the Hyperborean Land, and across the Middle East to India. What has not been illustrated is the presence of the Amanita symbols in the classic Buddhist Legend of Shambhala, which will be explicated in this presentation.
Elyse studied Greek philosophy, mythology and Eastern religions before moving north to go to UC Berkeley in 1966, but subsequently “dropped out,” joining the subculture experimenting with psychedelics in San Francisco. She began practicing Zen Buddhism at the SF Zen Center, and in 1969 went to Europe and then overland to India/Nepal in 1971. She returned to India in 1973 and studied Tibetan Buddhism in Nepal and Dharmsala, residence of the Dalai Lama, for 1 ½ years. She then moved to Madison WI to study with Geshe Sopa for 8 years. In 1981 she finished her BA in South Asian Studies at the University of Madison, WI taking mostly graduate courses in the Buddhist Studies Dept. In 1983 she received a Masters degree in Social Work with a clinical focus. After returning to the West coast, she studied with various Jungian Psychologists while continuing studies of Tibetan Buddhism. Elyse worked in Community Mental Health till 2006 while doing some private practice in the East Bay. She is now retired to Lake County, CA where she is writing and has a private psychotherapy practice.
Psilocybe allenii: A New Bluing Species from the Pacific Coast, USA
Cannabinoid Augmentation of Extinction Learning
Wars overseas have dramatically increased the number of new cases of PTSD. As existing pharmacological therapies have only limited efficacy, and none are curative, there is an urgent need to develop new approaches for PTSD treatment. This proposed study is the first step toward development of a novel new approach based on the cannabinoid neurotransmitter system.
PTSD is characterized by deficits in extinction learning, which may directly contribute to the “re-experiencing” symptom cluster of PTSD and indirectly to avoidance of triggers. Extinction learning is the process by which an association between a cue (CS+) and a unconditioned stimulus (US) is eliminated—as, for example, when Pavlov rang a bell but did not give food to his dogs, causing them eventually to stop salivating. It is not simply “forgetting”, but rather represents a parallel and opposite learning process that overrides the original conditioning. The endocannabinoid system is critical for extinction learning, and the effects of brain cannabinoid receptor (CB1) receptor activation on fear extinction have been robustly demonstrated in animals. CB1 receptor activation enhances extinction learning, and CB1 receptor blockade impairs it. CB1 receptors can be activated either by the exogenous CB1 agonist Δ9-tetrahydrocannabinol (THC), or by the endogenous CB1 agonist anandamide. Thus, the enhancement of extinction learning by either exogenous administration of cannabinoids or by boosting intrinsic endocannabinoid levels (thus activating CB1 receptors) can be harnessed to counteract persistent maladaptive associative learning such as aversive conditioning, which is directly relevant to PTSD.
This study proposes to manipulate the cannabinoid system and thus show that activation of the cannabinoid system enhances extinction learning by testing two mechanisms for activating CB1 receptors. The first is by enhancing endogenous cannabinoid levels by inhibiting one of the enzymes that degrades endocannabinoids, fatty acid amide hydrolase (FAAH). The second is by administering an exogenous cannabinoid agonist.
Study design: We propose to evaluate the efficacy of both the FAAH inhibitor PF-04457845 and the CB1 receptor agonist THC in a laboratory model of extinction learning in healthy subjects and also in veterans with PTSD. An initial study in healthy subjects will validate the methodology and gather data on the safety of both drugs used in this fashion before we proceed with veterans with PTSD. THC can serve as an “active control”, as it has been tested in other studies to augment extinction learning, whereas PF-04457845 has not.
Extinction learning will be tested by pairing a neutral cue (CS+: colored square) with an aversive stimulus (US: mild electric shock), extinguishing the association after administering the study medication, then measuring extinction recall on a third day. The primary outcome measures will be autonomic measures of stress response: skin conductance (SCR), acoustic startle reflex, salivary amylase, and serum cortisol. Subjects will be randomized to one of three parallel arms: placebo, PF-04457845, or THC.
Hypothesis #1: Both administration of PF-04457845 and THC will facilitate extinction learning and extinction retention (persistence of extinction learning) in healthy normal subjects and in veterans with PTSD.
Showing that extinction learning is augmented by either approach to activating CB1 (exogenous cannabinoid administration or endocannabinoid enhancement) will provide validation of animal models that show that CB1 receptor activation via exogenous cannabinoid administration (THC) and endocannabinoid enhancement both augment extinction learning, and substantiate the development of treatments for PTSD based on the CB1 receptor.
After graduating with a BA in Physics from Cornell University, Dr. Sewell pursued his interest in entheogens the medical route by obtaining an MD from the University of Connecticut School of Medicine in 1998 then completing a combined residency in Neurology and Psychiatry at the University of Massachusetts School of Medicine in 2004, where he served as Chief Resident in Neuropsychiatry. Following this, he attended a substance abuse research fellowship at McLean Hospital/Harvard Medical School, where he served as Managing Editor of the McLean Annals of Behavioral Neurology. He also published the first paper ever on the response of cluster headache to psilocybin and LSD, presenting the data both at the American Psychiatric Association Annual Meeting and the International LSD Symposium in Basel in 2006. He followed this with a discussion of the effect of LSA-containing seeds on cluster headache at the 2008 World Psychedelic Forum. For the last five years he has worked at Yale University in the Schizophrenia Research Group under Dr. Cyril D'Souza, studying the effects of psychotropic agents such as Δ9-THC, amphetamine, iomazenil, and salvinorin A in human subjects. His research interests include the mechanisms and characterization of psychosis (both induced and in schizophrenia), therapeutic applications of cannabinoids and entheogens, and the pathophysiology and treatment of cluster headache. Dr. Sewell is board-certified in both neurology and psychiatry, and serves on the Erowid Expert Network.
Role of Mesolimbic 5-HT2C/A Receptors in Opiate Withdrawal Motivation in Animal Models of Addiction
Evidence from our laboratory suggests that the rewarding effects of opiates are mediated by two separate reward substrates, dependent upon the motivational state of the animal. Chronic exposure to opiates produces molecular and cellular adaptations in ventral tegmental area (VTA) neurons, which are critical neural substrates for the motivational properties of opiates. Brain-derived neurotrophic factor (BDNF) has been reported to act in the VTA to mediate long-term molecular, cellular, and behavioural adaptations associated with drug dependence and the withdrawal state. It has been suggested that BDNF, a growth factor expressed after chronic drug intake, induces the transition to a drug-dependent motivational state, a crucial issue in drug addiction research. Furthermore, recent findings show that the aversive effects of acute and chronic morphine withdrawal and the opioid antagonist naloxone were blocked in both dependent and naive animals when the BDNF signaling was depleted in the VTA. We have suggested that withdrawal from opiates progressively leads to BDNF mediated physiological aversive changes in the VTA that drive and maintain addiction through a negative reinforcement mechanism.
There is growing evidence suggesting that the 5-hydroxytryptamine type 2C/A (5-HT2C/A) receptor regulates the expression of BDNF in the brain. Also, several studies in human and animal models imply that 5-HT2C/A agonists (e.g., Psilocybin, LSD-25, Ibogaine, etc.) have therapeutic utility in the treatment of obesity, depression, anxiety, obsessive-compulsive disorder and drug addiction. We hypothesize that a 5-HT2C/A agonist will decrease the expression of BDNF in the VTA, blocking the opiate reward switching mechanism from a drug-naive to drug-dependent/withdrawn motivational system.
In this study, using an unbiased place-conditioning paradigm, we examined the role of 5-HT2C/A agonists on morphine withdrawal motivation. Rats received the 5-HT2C/A receptor agonists N,N-Dimethyltryptamine (DMT) by means of intraperitonial administration (i.p) (2mg/kg) or Diethyltryptamine (DET) by bilateral VTA cannulae microinjections (1.5 ug). Our results show that i.p. injections of DMT produce a robust place aversion. However the aversive effects of acute morphine withdrawal and the opioid antagonist, naloxone, were blocked in naïve animals by DMT and DET administrations. These results show that although DMT and DET administration can produce aversive motivational effects, they are able to relieve the aversive motivational state produced by opiate withdrawal. Our results suggest that 5-HT2C/A agonists could be used as a therapeutic agent against the aversive effects produced by opiate withdrawal.
Dr. Hector Vargas-Perez is a Postdoctoral Fellow under the supervision of Dr. Derek van der Kooy in the Department of Molecular Genetics at the University of Toronto. He is a biologist that received a M.Sc. in Cognitive Neurosciences and a Ph.D. in Biomedical Sciences at the Institute of Neurobiology of the National University of Mexico. His research career has focused on understanding how animals choose behavior from several courses of action through behavioural, physiological, and molecular assays. Currently, he is uncovering the specific temporal changes in mesolimbic brain circuits, which occur following initial and repeated psychoactive-drug exposure and underscore the motivation of drug abuse. His current and prospective research interests are focused on the study of neuronal adaptations in motivational reward pathways associated with aversive motivation and potential therapeutics for stress-related diseases.
Use of Cannabis to Treat Symptoms of Anxiety and Depression: Results from a Survey of Canadian Medical Cannabis Users
This study examined the use of cannabis as a treatment for symptoms of anxiety and depression among a diverse sample of medical cannabis users. Participants were 605 self-selected Canadian adults who endorsed current use of cannabis for therapeutic purposes. Participants completed an online or in-person survey that queried attitudes and behaviors associated with medical cannabis use, and mental and physical health. Questions were embedded within the larger Cannabis Access for Medical Purposes Survey (CAMPS). The use of cannabis to treat symptoms of depression or anxiety was endorsed by 84% of participants; 61% reported using cannabis to treat both anxiety and depression,18% to treat anxiety symptoms only, and 5% reported using cannabis to treat symptoms of depression only. Anxiety and/or depression were identified as the primary medical condition for which cannabis was used by 18% of respondents. The use of cannabis to treat symptoms of anxiety and or depression was relatively stable across the 82% of participants for whom mood/anxiety disorders were not primary conditions; the only observed difference was a relatively lower rate (64%) of cannabis use to treat anxiety symptoms among patients who identified arthritis as their primary medical condition. The use of cannabis for depression/anxiety symptoms was also consistent across gender, and across federally authorized and unauthorized users. The findings of this cross-sectional study indicate that cannabis is widely used for its concurrent anxiolytic and/or antidepressant effects across diverse groups of medical cannabis users. This suggests that cannabis may be a valuable complement to address psychological symptoms that often accompany, and may complicate, other medical conditions. Further research is warranted to better characterize the distinct and interactive importance of the anxiolytic, antidepressant, and other therapeutic effects of cannabis.
Zach Walsh, PhD, is an Assistant Professor in the University of British Columbia Department of Psychology, Co-Director for the Centre for the Advancement of Psychological Science and Law, and a registered clinical psychologist. Zach’s cannabis-related research focuses on the use of cannabis for therapeutic and recreational purposes, and on the associations among cannabis use, mental health and addictions. Ongoing externally funded projects include the Cannabis Access for Medical Purposes Study (CAMPS) designed to identify barriers to access for medical cannabis; the Medical Cannabis Standards Engagement Evaluation and Dissemination (SEED) study which is a partnership with the Canadian Association of Medical Cannabis Dispensaries to develop and implement a standardization and certification framework for medical cannabis dispensaries; and the Medical Cannabis and Arthritis - Barriers and Pathways study which will examine attitudes and behaviours related to the use of cannabis for therapeutic purposes among individuals with arthritis. Zach and his colleagues are also involved in research specifying the role of mood and cognition in the analgesic effects of cannabis, clarifying relationships between cannabis use and the use of other psychoactive substances, and investigations of cannabis use trajectories among university students.
Psychedelic Harm Reduction: Psychometric Assessment of Substance-Related Risks with the Heidelberg Drug Questionnaire
Jan Weinhold, PhD, studied psychology at the Humboldt-University Berlin. Since 2002, he has been working as a research psychologist within the Collaborative Research Centre "Dynamics of Ritual" (SFB 619 "Ritualdynamik") at Heidelberg University, where he completed his PhD in 2011. His research covers the use of psychoactive substances in relation to ritual studies, drug-abuse prevention, cross-cultural psychology, altered states of consciousness, and systemic psychotherapy. He has published articles in the field of ritual studies and drug use and has co-edited the volumes Rituals on the Move [Rituale in Bewegung] (LIT-Verlag, 2006), Therapy With Psychoactive Substances: Approaches to and Critique of Psychotherapy with LSD, Psilocybin, and MDMA [Therapie mit psychoaktiven Substanzen: Praxis und Kritik der Psychotherapie mit LSD, Psilocybin und MDMA] (Huber, 2008), The Problem of Ritual Efficacy (Oxford University Press, 2010), and The Varieties of Ritual Experience (Harrassowitz, 2010).