N,N-Dimethyltryptamine (DMT) is an indole alkaloid widely found in plants and animals. It is best known for producing brief and intense psychedelic effects when ingested. Increasing evidence suggests that endogenous DMT plays important roles for a number of processes in the periphery and central nervous system, and may act as a neurotransmitter. This paper reviews the current literature of both the recreational use of DMT and its potential roles as an endogenous neurotransmitter. Pharmacokinetics, mechanisms of action in the periphery and central nervous system, clinical uses and adverse effects are also reviewed. DMT appears to have limited neurotoxicity and other adverse effects except for intense cardiovascular effects when administered intravenously in large doses. Because of its role in nervous system signaling, DMT may be a useful experimental tool in exploring how brain works, and may also be a useful clinical tool for treatment of anxiety and psychosis.
Carbonaro, T. M., & Gatch, M. B. (2016). Neuropharmacology of N, N-Dimethyltryptamine. Brain Research Bulletin. http://dx.doi.org/10.1016/j.brainresbull.2016.04.016
Evidence suggests that hallucinogens may have therapeutic potential for addressing a variety of problem behaviors related to the externalizing spectrum of psychopathology, such as substance misuse and criminality. Intimate partner violence (IPV) is a prevalent form of criminal violence that is related to externalizing pathology. However, the association between hallucinogen use and IPV has not been comprehensively examined. In this prospective study, we examined the association between IPV and naturalistic hallucinogen use among 302 inmates at a US county jail. Cox regression analyses indicated that hallucinogen use predicted reduced arrest for IPV independently (β=−0.54, SE=0.20, χ2=7.19, exp(B)=0.58, p<0.01) and after accounting for covariates (β=−0.48, SE=0.23, χ2=4.44, exp(B)=0.62, p<0.05). These results add to a growing literature suggesting distinct therapeutic potential for hallucinogens to assist in the attenuation of problematic behavior.
Walsh, Z., Hendricks, P. S., Smith, S., Kosson, D. S., Thiessen, M. S., Lucas, P., & Swogger, M. T. (2016). Hallucinogen use and intimate partner violence: Prospective evidence consistent with protective effects among men with histories of problematic substance use. Journal of psychopharmacology (Oxford, England). http://dx.doi.org/10.1177/0269881116642538 Link to full text
Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests a single sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine may work to correct these neuroadaptations and restore motivation for non-drug rewards. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs money later, we found that ketamine, as compared to the control, significantly decreased cocaine self-administration by 67% relative to baseline at greater than 24 h post-infusion, the most robust reduction observed to date in human cocaine users and the first to involve mechanisms other than stimulant or dopamine agonist effects. These findings signal new directions in medication development for substance use disorders.
Dakwar, E., Hart, C. L., Levin, F. R., Nunes, E. V., & Foltin, R. W. (2016). Cocaine self-administration disrupted by the N-methyl-D-aspartate receptor antagonist ketamine: a randomized, crossover trial. Molecular Psychiatry. http://dx.doi.org/10.1038/mp.2016.39 Link to full text
Social ties are crucial for physical and mental health. However, psychiatric patients frequently encounter social rejection. Moreover, an increased reactivity to social exclusion influences the development, progression, and treatment of various psychiatric disorders. Nevertheless, the neuromodulatory substrates of rejection experiences are largely unknown. The preferential serotonin (5-HT) 2A/1A receptor agonist, psilocybin (Psi), reduces the processing of negative stimuli, but whether 5-HT2A/1A receptor stimulation modulates the processing of negative social interactions remains unclear. Therefore, this double-blind, randomized, counterbalanced, cross-over study assessed the neural response to social exclusion after the acute administration of Psi (0.215 mg/kg) or placebo (Pla) in 21 healthy volunteers by using functional magnetic resonance imaging (fMRI) and resting-state magnetic resonance spectroscopy (MRS). Participants reported a reduced feeling of social exclusion after Psi vs. Pla administration, and the neural response to social exclusion was decreased in the dorsal anterior cingulate cortex (dACC) and the middle frontal gyrus, key regions for social pain processing. The reduced neural response in the dACC was significantly correlated with Psi-induced changes in self-processing and decreased aspartate (Asp) content. In conclusion, 5-HT2A/1A receptor stimulation with psilocybin seems to reduce social pain processing in association with changes in self-experience. These findings may be relevant to the normalization of negative social interaction processing in psychiatric disorders characterized by increased rejection sensitivity. The current results also emphasize the importance of 5-HT2A/1A receptor subtypes and the Asp system in the control of social functioning, and as prospective targets in the treatment of sociocognitive impairments in psychiatric illnesses.
Preller, K. H., Pokorny, T., Hock, A., Kraehenmann, R., Stämpfli, P., Seifritz, E., … & Vollenweider, F. X. (2016). Effects of serotonin 2A/1A receptor stimulation on social exclusion processing. Proceedings of the National Academy of Sciences, 201524187. http://dx.doi.org/10.1073/pnas.1524187113
Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75 µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC–visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.
Kaelen, M., Roseman, L., Kahan, J., Santos-Ribeiro, A., Orban, C., Lorenz, R., … & Wall, M. B. (2016). LSD modulates music-induced imagery via changes in parahippocampal connectivity. European Neuropsychopharmacology. http://dx.doi.org/10.1016/j.euroneuro.2016.03.018 Link to full text
Opnieuw hebben onderzoekers van het Psychedelic Research Programme, opgezet in samenwerking tussen de Beckley Foundation en het Londense Imperial College, baanbrekend onderzoek gepubliceerd naar de effecten van psychedelica op de hersenen. Deze trendsettende studies zijn de eerste waarbij multimodale neuro-beeldvorming is toegepast op deelnemers die met LSD waren geïnjecteerd. Gebruikmakend van fMRI BOLD, arterial spin labelling en magnetoencephalografie (MEG), hebben dr. Carhart-Harris en zijn collega’s van het Imperial College London de effecten van lysergeenzuurdi-ethylamide (LSD) op de netwerkcommunicatie, bloeddoorstroming en elektrische activiteit van de hersenen onthuld (Carhart-Harris et al., 2016).
Uit deze neuro-beeldvormingsonderzoeken hebben onderzoekers een nieuw en belangrijk inzicht gekregen in de basis van de ontbinding van het ego, de manier waarop ‘closed-eye visuals’ ontstaan en de effecten van de combinatie van LSD en muziek in het brein. De onderzoeken werden gedaan met 20 deelnemers die de ene keer 75µg LSD kregen ingespoten en de andere keer een placebo, met minstens twee weken er tussenin. Alle deelnemers hadden al ervaring met psychedelica.
Om de activiteit van verschillende hersengebieden en hun interconnecties gedurende LSD-invloed te evalueren, werd gebruik gemaakt van functional magnetic resonance imaging (fMRI), gebaseerd op de evaluatie van bloedzuurstofniveau-afhankelijk contrast (blood oxygen level dependent, ‘BOLD’). De scans werden uitgevoerd in een staat van rust, d.w.z. zonder externe stimuli of specifieke cognitieve taken. Daarna werden de niveaus van (des)integratie/(de)segregatie geëvalueerd, waarbij bepaalde interessante gebieden werden uitgelicht om hun interactie met de andere hersengebieden te analyseren.
Gemiddelde functionele connectiviteitsdichtheid (FCD) in corticale en subcorticale gebieden onder invloed van placebo en LSD – Tagliazucchi et al., 2016.
Een van de belangrijkste bevindingen uit het onderzoek was dat LSD een toename van geglobaliseerde communicatie tussen verschillende hersenregio’s bewerkstelligt. Door gebruik te maken van positron emissie tomografie (PET) ontdekten de onderzoekers dat het hoogste niveau van dergelijke communicatie plaatsvond in de gebieden met de hoogste dichtheid van serotonine-2A (5-HT2A) receptoren, aangezien LSD als een antagonist voor dit type receptoren werkt. Een interessant aspect hiervan is dat deze hogere interactie tussen hersengebieden overeenkomt met een lagere integratie binnen bepaalde netwerken. In totaal werden door de studie 12 ‘resting state networks’ geïdentificeerd die op deze manier door LSD werden beïnvloed, waarbij het defaultnetwerk (of default mode network, DMN) voor dit onderzoek het belangrijkste was.
Ontbinding van het ego
Het DMN is het netwerk in de hersenen dat geactiveerd wordt wanneer een persoon ruststaten zoals dagdromen ervaart, en gedeactiveerd raakt gedurende doelgerichte taken. Volgens het huidige onderzoek is de desintegratie binnen het DMN rechtstreeks gerelateerd aan het ontstaan van een bewustzijnstoestand die meestal wordt beschreven als een ontbinding van het ego. De ontbinding van het ego is de subjectieve ervaring van het verliezen van het gevoel van identiteit. Het wordt ook wel beschreven als eenheid met de buitenwereld of met het universum, voortgebracht door het vervagen van de grenzen van het autonome zelf. De vragenlijst over veranderde staten van bewustzijn die aan het eind van elke scandag werd gebruikt, onthulde dat de ontbinding van het ego gecorreleerd is aan de ervaring van veranderde betekenis, i.e. het hechten van belang aan objecten die eerder onbelangrijk werden geacht en het verlenen van een nieuwe, vreemde betekenis aan de omgeving. Ook andere hersengebieden, zoals het salience netwerk en de thalamus, werden in verband gebracht met de staat van ego-ontbinding.
Hersengebieden waar een significante correlatie werd gevonden tussen FCD en subjectieve meldingen van ego-ontbinding (LSD min placebo) staan rood gekleurd. Hersengebieden waar zich de meest selectieve correlaties voordoen tussen toenames van FCD en scores voor ego-ontbinding staan groen gekleurd – Tagliazucchi et al., 2016
De desintegratie van het DMN en andere rust-netwerken ging tevens gepaard met een verzwakking van de alfa hersengolven in gebieden zoals de cortex cingularis posterior (of posterior cingulate cortex / PCC). Over reguliere alfagolven bestaat de hypothese dat ze spontane neurale activiteit, d.w.z. die zonder blootstelling aan stimuli optreedt, tegenhouden (Tagliazucchi et al., 2016). Het bleek dat LSD de alfakracht doet afnemen en daarmee spontane activiteit in neuronen veroorzaakt, een effect dat de visuals bij gesloten ogen, die gepaard gaan met de LSD-ervaring, deels zou kunnen verklaren.
De werking van visuals bij gesloten ogen
In het onderzoek naar door LSD opgeroepen closed-eye visuals werden opvallende resultaten binnengehaald. De onderzoekers keken zowel naar eenvoudige beelden zoals geometrische patronen, als naar complexe beelden, waaronder autobiografische scènes, die zich onder LSD voordeden. Het onderzoek toonde aan dat, ook al was er geen visuele input, de visuele cortex (VC) zich onder invloed van LSD toch gedroeg alsof die er wel was (Carhart-Harris et al., 2016). Deze observatie ondersteunt huidige theorieën die zeggen dat het verschijnen van geometrische beelden wellicht veroorzaakt wordt door de opgewekte instabiliteit van de VC (Butler et al., 2011).
Naast een toename in het niveau van bloeddoorstroming vertoonde de VC ook een toegenomen functionele connectiviteit met andere hersendelen, met name de cortex parahippocampalis (of PHC), die betrokken is bij het oproepen van herinneringen, door muziek veroorzaakte emoties, en mentale beeldvorming. De onderzoekers gebruikten een Dynamic Causal Modelling-analyse om een toegenomen effectieve connectiviteit tussen de VC en de PHC aan te tonen, waarbij de PHC de activiteit van de VC veroorzaakte. De verwevenheid van deze hersengebieden kan verantwoordelijk worden gehouden voor het ‘kleuren’ van persoonlijke herinneringen die de deelnemers onder LSD ervoeren. Naast de PHC werden andere hersenregio’s zoals die in de occipitale en inferiore frontale kwab ook geactiveerd, wat tot de conclusie leidt dat onder invloed van LSD een veel groter deel van de hersenen betrokken is bij het voortbrengen van beelden dan in de normale waaktoestand.
De invloed van muziek
Veder kwam het grote belang van muziek tijdens de psychedelische ervaring uit het onderzoek naar boven. Mendel Kaelen, promovendus aan het Imperial College London en directielid van Stichting OPEN, onderzocht de synergistische effecten van muziek tijdens de LSD-ervaring (Kaelen et al., 2016). Er werden drie fMRI-scans uitgevoerd, de eerste en derde zonder muziek, en de tweede terwijl de deelnemers naar muziek luisterden (twee fragmenten uit het album Yearning van de ambient artiest Robert Rich en de Indische klassieke muzikante Lisa Moscow).
Het onderzoek liet zien dat de PHC hevig geactiveerd raakt wanneer deelnemers aan muziek en LSD blootgesteld worden. Bovendien correspondeerde de toename van interactie tussen de PHC en de visuele cortex met de intensiteit van de closed-eye visuals, zowel de eenvoudige (geometrische patronen) als de complexe (bv. gebaseerd op persoonlijke herinneringen). Dit benadrukt het belang van het verwerken van muziek in LSD-ondersteunde therapie.
Kennis uitbreiden
De bevindingen van dit onderzoek met LSD verstevigen de basis van de kennis die vergaard is in experimenten met andere psychedelica. Van psilocybine is aangetoond dat het vergelijkbare effecten heeft op hersenactiviteit, met inbegrip van de desintegratie in bepaalde gebieden zoals het defaultnetwerk en het ontstaan van nieuwe verbindingen tussen netwerken die normaliter gesegregeerd zijn. Deze conclusies kwamen voort uit twee onafhankelijke onderzoeken, waarvan er één werd uitgevoerd door de auteurs van het onderhavige LSD-onderzoek (Carhart-Harris et al., 2012, Kometer et al., 2015). Weer een andere onderzoeksgroep ontdekte soortgelijke effecten op de menselijke hersenen van ayahuasca, een psychedelicum uit het Amazonegebied (Riba et al., 2002).
De resultaten van dit baanbrekende onderzoek hebben een aantal belangrijke implicaties. Ten eerste geven ze een begin van neurologisch inzicht in het therapeutisch potentieel van LSD. Door zijn ‘entropische’ effect op de hersenen – de toename van desintegratie binnen en tegelijkertijd toename van interactie tussen bepaalde hersengebieden – heeft LSD potentieel om pathologische patronen, die worden geassocieerd met bijvoorbeeld depressie, af te breken, en zo de effectiviteit van psychotherapie te vergroten.
Het onderzoek heeft tevens aangetoond dat LSD potentieel heeft om van nut te zijn bij de studie naar de neurobiologie van het bewustzijn, gezien het feit dat het deelnemers in de zogenaamde ‘primitieve bewustzijnstoestand’ lijkt te brengen, die karakteristiek is voor de vroege stadia van bewustzijnsontwikkeling in kinderen, voor REM-slaap en voor de beginfase van psychose (Carhart-Harris et al., 2016). Dit betekent ook dat LSD zou kunnen worden toegepast in psychologische studies in het onderzoek naar pathologieën (Carhart-Harris et al., 2016).
Naast de korte-termijneffecten van LSD op de hersenchemie is tevens meer onderzoek nodig naar het potentieel van LSD-ervaringen om blijvende persoonlijkheidsveranderingen teweeg te brengen.
Butler T. C., Benayoun M., Wallace E., van Drongelen W., Goldenfeld N. and Cowan J. (2012). Evolutionary constraints on visual cortex architecture from the dynamics of hallucinations. Proceedings of the National Academy of Sciences of the United States of America, 606-609. https://dx.doi.org/10.1073/pnas.1118672109
Carhart-Harris R. L., Errizoe D., Williams T., Stone J. M., Reed L. J., Colasanti A., Tyacke R.J., Leech R., Malizia A.L., Murphy K., Hobden P., Evans J., Feilding A., Wise R.G. and Nutt D.J. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc. Natl. Acad. Sci. USA 109, 2138–2143. https://dx.doi.org/10.1073/pnas.1119598109
Carhart-Harris R. L., Muthukumaraswarmy S., Roseman L., Kaelen M., Droog W., Murphy K., Taggliazzuchi E., Schenberg E.E., Nest T., Orban C., Leech R., Williams, L., Williams T., Bolstridge M., Sessa B., McGoniglea J., Sereno M., Nichols D., Hellyer P.J., Hobden P., Evans J., Singh K.D., Wise R.G., Curran V., Feilding A. and Nutt D.J. (2016) Neural Correlates of the LSD Experience Revealed by Multimodal Neuroimaging. Proceedings of the National Academy of Sciences of the United States of America, 1-6. https://dx.doi.org/10.1073/pnas.1518377113
Kaelen M., Roseman L., Kahan J., Santos-Ribeiro A., Orban C., Lorenz R., Barett F.S., Bolstridge M., Williams T., Williams L., Wall M.B., Feilding A., Muthukumuraswamy S., Nutt D.J and Carhart-Harris, R. (2016) LSD modulates music-induced imagery via changes in the parahippocampal connectivity. European Neuropsychopharmacology, 1-10. http://dx.doi.org/10.1016/j.euroneuro.2016.03.018
Kometer M., Pokorny T., Seifritz E. and Vollenweider F.X. (2015) Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations. Psychopharmacology (Berl) 232(19):3663–3676. https://dx.doi.org/10.1007/s00213-015-4026-7
Tagliazucchi E., Roseman L., Kaelen M., Orban C., Muthukumaraswamy S. D., Murphy K., Laufs H., Leech R., McGonigle J., Crossley N., Bullmore E., Williams T., Bolstridge M., Feilding A., Nutt D.J. and Carhart-Harris R. (2016). Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology, 26, 1-8. http://dx.doi.org/10.1016/j.cub.2016.02.010
Once again researchers from the Psychedelic Research Programme jointly set up by the Beckley Foundation and Imperial College London have published trailblazing research on the effects of psychedelics on the brain. These trendsetting studies are the first to apply multimodal neuroimaging to subjects who were injected with LSD. Dr. Carhart-Harris and his fellow colleagues from Imperial College London have revealed the effects of lysergic acid diethylamide (LSD) on the brain’s network communication, blood flow and electrical activity using fMRI BOLD, arterial spin labelling and magnetoencephalography (Carhart-Harris et al., 2016).
From these neuroimaging studies, researchers have gained an important and novel insight into the basis of ego-dissolution, the way in which closed-eye visuals occur and effects of the combination of LSD and music in the brain. The studies were conducted with 20 subjects who were injected once with 75µg LSD and once with a placebo, at least two weeks apart. All participants had prior experience with psychedelics.
Functional magnetic resonance imaging (fMRI) based on the evaluation of blood oxygen level dependent (BOLD) contrast was applied to evaluate the activity of different brain regions and their interconnection while on LSD. The scans were performed in the resting state, i.e. in the absence of any external stimuli or specific cognitive tasks. Subsequently the levels of (dis)integration/(de)segregation were evaluated, with certain regions of interest (ROI) being picked up to analyse their interaction with the other brain regions.
Average functional connectivity density (FCD) in cortical and subcortical regions under the placebo and LSD conditions – Tagliazucchi et al., 2016.
One of the main findings of the study was that LSD facilitates an inflation of globalised communication between various brain regions. Using positron emission tomography (PET), the researchers found that the highest level of such communication occurred in the regions with the highest density of serotonin-2A (5-HT2A) receptors, LSD acting as an agonist to this type of receptors. One interesting aspect of this is that the higher interaction between brain regions corresponded with lower integration within certain networks. All in all, the study identified 12 resting state networks affected by LSD in this way, with the default mode network (DMN) being the most important for the case at study.
Ego dissolution
The DMN is the network of the brain that becomes activated when a person is experiencing resting states such as daydreaming, and becomes inactivated during goal-oriented tasks. According to the present study, the disintegration within the DMN is directly related to the onset of a state of consciousness commonly described as ego dissolution. Ego dissolution is the subjective experience of losing one’s sense of identity. It is sometimes described as unity with the outside world and oneness with the universe resulting from a blurring of the boundaries of the autonomous self. The altered state of consciousness questionnaire used at the end of each scanning day revealed that ego dissolution correlated with the experience of altered meaning, i.e. attaching importance to objects previously deemed unimportant and giving surroundings new, alien meaning. Also correlated with the state of ego dissolution was disintegration in other brain regions such as the salience network and the thalamus.
Brain regions where a significant correlation between FCD and subjective reports of ego dissolution (LSD minus placebo) was found are colored in red. Brain regions presenting the most selective correlations between FCD increases and ego dissolution scores are colored in green – Tagliazucchi et al., 2016
Disintegration in the DMN and other resting networks was also accompanied by decreased alpha power in regions such as the posterior cingulate cortex (PCC). Regular alpha oscillations are hypothesised to inhibit spontaneous neuronal activity, i.e. that which occurs without exposure to particular stimuli (Tagliazucchi et al., 2016). LSD was found to decrease alpha power and thus trigger spontaneous activity in neurons, an effect that could partially explain the closed-eye imagery associated with the LSD experience.
The mechanisms of closed-eye imagery
Striking results were obtained in the study of closed-eye imagery induced by LSD. The researchers investigated both simple images like geometrical patterns and complex ones including autobiographical scenes occurring under LSD. The study revealed that although there was no visual input, under LSD the visual cortex (VC) behaved as if there was (Carhart-Harris et al., 2016). This observation supports ongoing theories that the appearance of geometrical imagery may be caused by the rendered instability of the VC (Butler et al., 2011).
Apart from the increase in blood flow level, the visual cortex also displayed increased functional connectivity with other brain regions, mainly the parahippocampal cortex (PHC), typically involved in memory retrieval, music-evoked emotion and mental imagery. The researchers used a Dynamic Causal Modelling analysis to reveal increased effective connectivity between the VC and the PHC, where the PHC triggered the activity of the VC. The interconnection of these brain regions can be held responsible for the “colouring” of personal recollections experienced by the subjects under LSD. Apart from the PHC, other brain regions such as those in occipital and inferior frontal lobes also became activated during visuals, leading to the conclusion that a much larger portion of the brain is involved in producing imagery under LSD than in the normal waking state.
The influence of music
The study further revealed the highly important role of music during the psychedelic experience. Mendel Kaelen, a PhD candidate at Imperial College London and board member of the OPEN Foundation, explored the synergistic effects of music during the LSD experience (Kaelen et al., 2016). Three fMRI scans were performed, the first and the third of which were done without the use of music, the second being performed while the subjects listened to music (two excerpts from the album Yearning by the ambient artist Robert Rich and the Indian classical musician Lisa Moscow).
The study showed that the PHC becomes highly activated when subjects are exposed to music and LSD. Furthermore, the increase of interaction between the PHC and the visual cortex corresponded with the intensity of the closed-eye visuals, both simple (geometrical patterns) and complex ones (e.g. based on personal recollections). This certainly underscores the importance of incorporating music into LSD-assisted psychotherapy.
Expanding the knowledge
The findings of the present study with LSD provide firmer ground to the knowledge that has been gathered in experiments using other psychedelics. Psilocybin has been found to have similar effects on brain activity including the disintegration in certain regions such as the default mode network and the emergence of new connections between normally segregated networks. These conclusions emerged from two independent researches, one of which was performed by the authors of the present LSD study (Carhart-Harris et al., 2012, Kometer et al., 2015). Still another research group discovered analogous effects of the Amazonian psychedelic ayahuasca on the human brain (Riba et al., 2002).
The findings of this groundbreaking study have several important implications. First, they hint at a neurological understanding of the therapeutic potential of LSD. Due to its “entropic” effect on the brain – the increase of disintegration within and simultaneous increase of interaction between certain brain regions – LSD may hold the potential for breaking down pathological patterns associated with depression, for instance, and thus increasing the effectiveness of psychotherapy.
The study also demonstrated the potential of LSD in the study of the neurobiology of consciousness, as it seems to put subjects into the so-called primary state of consciousness characteristic of the earlier stages of consciousness development in children, of REM sleep and of early psychosis (Carhart-Harris et al., 2016). This also means that LSD could be applied in psychological research in the study of pathologies (Carhart-Harris et al., 2016).
Apart from the short-term effects of LSD on brain chemistry, more investigation is warranted on the potential of the LSD experience to provoke sustainable changes in personality.
Butler T. C., Benayoun M., Wallace E., van Drongelen W., Goldenfeld N. and Cowan J. (2012) Evolutionary constraints on visual cortex architecture from the dynamics of hallucinations. Proceedings of the National Academy of Sciences of the United States of America, 606-609. https://dx.doi.org/10.1073/pnas.1118672109
Carhart-Harris R. L., Errizoe D., Williams T., Stone J. M., Reed L. J., Colasanti A., Tyacke R.J., Leech R., Malizia A.L., Murphy K., Hobden P., Evans J., Feilding A., Wise R.G. and Nutt D.J. (2012) Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc. Natl. Acad. Sci. USA 109, 2138–2143. https://dx.doi.org/10.1073/pnas.1119598109
Carhart-Harris R. L., Muthukumaraswarmy S., Roseman L., Kaelen M., Droog W., Murphy K., Taggliazzuchi E., Schenberg E.E., Nest T., Orban C., Leech R., Williams, L., Williams T., Bolstridge M., Sessa B., McGoniglea J., Sereno M., Nichols D., Hellyer P.J., Hobden P., Evans J., Singh K.D., Wise R.G., Curran V., Feilding A. and Nutt D.J. (2016) Neural Correlates of the LSD Experience Revealed by Multimodal Neuroimaging. Proceedings of the National Academy of Sciences of the United States of America, 1-6. https://dx.doi.org/10.1073/pnas.1518377113
Kaelen M., Roseman L., Kahan J., Santos-Ribeiro A., Orban C., Lorenz R., Barett F.S., Bolstridge M., Williams T., Williams L., Wall M.B., Feilding A., Muthukumuraswamy S., Nutt D.J and Carhart-Harris, R. (2016) LSD modulates music-induced imagery via changes in the parahippocampal connectivity. European Neuropsychopharmacology, 1-10. http://dx.doi.org/10.1016/j.euroneuro.2016.03.018
Kometer M., Pokorny T., Seifritz E. and Vollenweider F.X. (2015) Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations. Psychopharmacology (Berl) 232(19):3663–3676. https://dx.doi.org/10.1007/s00213-015-4026-7
Riba J., Anderer P., Morte A., Urbano G., Jané F., Saletu B. and Barbanoj M.J. (2002) Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers. Br J Clin Pharmacol 53(6):613–628. https://dx.doi.org/10.1046/j.1365-2125.2002.01609
Tagliazucchi E., Roseman L., Kaelen M., Orban C., Muthukumaraswamy S. D., Murphy K., Laufs H., Leech R., McGonigle J., Crossley N., Bullmore E., Williams T., Bolstridge M., Feilding A., Nutt D.J. and Carhart-Harris R. (2016) Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology, 26, 1-8. http://dx.doi.org/10.1016/j.cub.2016.02.010
Harmine is a β-carboline alkaloid present at highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 57%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY) and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of Dyrk1a is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Harmine also increased dendritic arborization, including total neurite length, number of segments, extremities and nodes in MAP2 positive neurons. Our findings show that harmine enhances neurogenesis of hNPCs in vitro, and suggest a biological activity associated with its antidepressant effects in vivo.
Dakic, V., de Moraes Maciel, R., Drummond, H., Nascimento, J. M., Trindade, P., & Rehen, S. K. (2016). Harmine stimulates neurogenesis of human neural cells in vitro (No. e1957v1). PeerJ Preprints. https://doi.org/10.7287/peerj.preprints.1957v1 Link to full text
Psychoactive drug use occurs in essentially all human societies. A range of disciplines contribute to our understanding of the influence of drugs upon the human world. For example pharmacology and neuroscience analyse biological responses to drugs, sociology examines social influences upon people’s decisions to use drugs, and anthropology provides rich accounts of use across a variety of cultural contexts. This article reviews work from multiple disciplines to illustrate that drugs influence aspects of culture from social life to religion, politics to trade, while acting as enablers of cultural change throughout human history. This broad view is valuable at a time when the influence not only of traditional drugs but a growing armoury of novel drugs is felt and debated.
Wadley, G. (2016). How psychoactive drugs shape human culture: a multi-disciplinary perspective. Brain Research Bulletin. http://dx.doi.org/10.1016/j.brainresbull.2016.04.008 Link to full text
interested in becoming a trained psychedelic-assisted therapist?
