Psychedelic Science

Curse or salvation?

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Psychedelic Ancient Greek words psychē (ψυχή, "soul") and dēloun (δηλοῦν, "to make visible, to reveal"), translating to “soul- or mind-revealing or –manifesting”

Synonyms: "hallucinogen", "psychotomimetic" "entheogen", (entheos “God/divine within”)

Hofmann first synthesized LSD on 16 November 1938 with intention to obtain a respiratory and circulatory stimulant. He was working for Sandoz Laboratories in Basel, Switzerland. On 16 April 1943 Hofmann decided to re-examine it. While re-synthesizing LSD, he accidentally touched his hand to his mouth, nose or possibly eye, accidentally ingesting a small amount and discovered its powerful effects.

Albert Hofmann (1906 –2008)

“... affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away.”

Albert Hofmann in 2006

Hofmann was active and continued his research until the last days of his life. He was due to speak at the World Psychedelic Forum from 21 to 24 March 2008 but was forced to cancel because of bad health. It was confirmed by a close co-worker that he was microdosing LSD for at least the last two decades of his life.

Between 1953 and 1973, the US federal government spent four million dollars to fund a hundred and sixteen studies of LSD, involving more than seventeen hundred subjects. (These figures don’t include classified research.) By the mid-nineteen-sixties, LSD had escaped from the laboratory and swept through the counterculture. In 1970, Richard Nixon signed the Controlled Substances Act and put most psychedelics on Schedule 1, prohibiting their use for any purpose. Research soon came to a halt, and what had been learned was all but erased from the field of psychiatry.

The research projects that were shut down in the late 1960’s are being replicated and furthered by institutes including Johns Hopkins, NYU, UCLA, UNM, University of Zurich and Imperial College, London and others around the world. So far there have been positive results for treating: nicotine addiction, alcoholism, depression and end-of-life anxiety and PTSD. The studies are not funded by traditional institutions, but by non-profit organisations: •MAPS (Multidisciplinary Association of Psychedelic Studies), •The Beckley Foundation and •Heffter Research Institute

"A pharma company needs to figure out how to make an obscene profit - that's what gets their attention. The problem is that these drugs are not addicting and you don't need to take them very often," (James Fadiman)

Psychedelic substances Serotonergic or classical psychedelics “tryptamines” (predominantly 5-HT2A receptor agonists): intense feelings of love, spirituality, “connectedness”, “oneness” with one’s surroundings, euphoria, altered visual and auditory sensory perceptions

LSD, LSA, psilocybin, DMT,

ibogaine (a “complex tryptamine”, an NDMA receptor antagonist, a K-opioid receptor agonist and 5HT2A receptor agonist, resulting in dissociative effects as well)

Empathogen-entactogens ”phentelamines” (serotonin releasers and 5HT2A agonists):

(feelings of openness, euphoria, empathy, love, heightened self-awareness, and by mild audio and visual distortions, an overall enhancement of sensory experience)

MDMA, MDEA, MDA, mescaline, mephedrone, 2C-B.

Dissociatives (NMDA antagonists)

(cause more intense de-realisation and de-personalisation)

ketamine

Atypical:

Salvia divinorum, salvinorin A (a K-opioid receptor agonist)

Effects are blocked by ketanserin (5HT2 receptor antagonist)

ketamine

Salvinorin A Morphine

The DMN “default mode network” • Regions: the posterior cingulate cortex; the medial prefrontal cortex; the

lateral inferior parietal cortex

• represents the anatomical basis of our sense of self, our experience of having an identity or self, and our capacity for introspection.

• This network has undergone significant evolutionary expansion.

• Significant ontogenetic development, from infancy to adulthood

• More metabolically active then elsewhere in the brain

• It serves as an important convergence zone or “connector hub” in the cortex.

• Activated during high-level thinking, such as predicting the future, making personal, social and moral judgments, and contemplating the past.

• Some assumption that the evolutionary development of the DMN is the biological basis for our psychological sense of “self” or “ego.”

• Overactive in depression and anxiety states

The TPN “task-positive network”

• Regions: the dorso-lateral parietal cortex; anterior cingulate and posterior parietal cortex

• Active when we attend to things in the external world (the “other”)

• It is in gear when we have externally focused attention, when we get wrapped up in getting something done and relatively forget about ourselves in the process

DMN and TPN

• The two modes of consciousness/networks do not, in ordinary waking consciousness, become activated simultaneously.

• The two networks exist side-by-side and in a somewhat competitive relationship

• Each becoming active when the need arises

• They alternate with extraordinary rapidity.

• They provide an alternative way we view human consciousness compare to left-right brain theory

Default Mode Network

Effects of psilocybin on DMN and TPN

• Significantly decreased activity in DMN

• Competitive activity breaks down between DMN

and TPN

• The two networks work as “one”

Magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality.

The study was conducted within the framework of the Beckley/Sant Pau Research Programme and in collaboration with the Spanish National Research Council. In the study participated the following researchers from the Spanish National Research Council (CSIC). They found that harmine and tetrahydroharmine, the alkaloids present in highest amounts in ayahuasca, stimulate the growth and maturation of neurons and promote their birth from the stem cells.

Amanda Feilding and David Nutt, co-directors of the Beckley/Imperial Research Programme

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

About the Study

This landmark study provides the first clinical evidence that psilocybin might help in the treatment of depression.

We gave oral psilocybin to 12 patients with treatment-resistant depression (meaning they had tried at least 2 other treatment methods and none had worked). The average length of depression was over 18 years, and severity ranged from moderate to severe. Participants received 2 doses (10 and 25mg) 7 days apart, accompanied by psychological support before, during, and after each session.

Following both sessions, all participants showed improvement in depressive symptoms. On standard measures of depression severity, 67% scored at levels considered ‘in remission’ (depression-free) 1 week after the treatment, and 42% were still in remission 3 months post-treatment.

Psilocybin in the Treatment of Depression. As a direct result of our previous studies examining the effects of psilocybin on the brain, the UK Medical Research Council awarded a substantial grant to the Beckley / Imperial Research Programme for a ground-breaking Phase I pilot study examining psilocybin as an aid to psychotherapy in the treatment of depression.

One dose of psilocybin outperformed sustained courses of both medication and psychotherapy, at 2 weeks and 3 months after

the dose - © R. Carhart-Harris, 2016

Connectivity within the brain, before (top) and after (bottom) a

dose of LSD- © R. Carhart-Harris, 2016.

• We’re talking about people suffering from anxiety and depression. The Default Mode Network is generally overactive in people with those disorders and Psilocybin has been shown to turn off the DMN and allow the brain to behave in ways never seen before. But we still know very little for certain. Isn’t that terrifying?

• “The point is we don’t know about it because no one has done it before. It’s quite fascinating. Getting some of this stuff published has been quite difficult. A lot of scientists would prefer if this whole thing went away. It raises challenges to philosophies and theories of science. It is like Einstein. We had a nice theory of physics and then suddenly relativity comes along and we have a different theory. Similarly we had a nice theory of consciousness but then our work comes along and says actually there’s another kind of psychedelic consciousness and that’s associated with very different brain activity.” (David Nutt, 52 Insights Magazine, Jan 2017)

• All of the 19 subjects who received MDMA-assisted treatment in the original trial participated in the long-term follow-up

• 16 out of 19 completing all of the long-term outcome measures, which were administered from 17 to 74 months after the original study’s final MDMA session

• subjects maintained statistically and clinically-significant gains in symptom relief, although two of these subjects did relapse.

“I thought the first ten or twenty people were plants—that they must be faking it. They were saying things like ‘I understand love is the most powerful force on the planet,’ or ‘I had an encounter with my cancer, this black cloud of smoke.’ People who had been palpably scared of death—they lost their fear. The fact that a drug given once can have such an effect for so long is an unprecedented finding. We have never had anything like it in the psychiatric field.” (Stephen Ross, associate professor of psychiatry at N.Y.U.’s medical school, director of the substance-abuse division at Bellevue)

Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5.

Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures DEBORAH C. MASH, CRAIG A. KOVERA, JOHN PABLO, RACHEL F. TYNDALE, FRANK D. ERVIN, IZBEN C. WILLIAMS, EDWARD G. SINGLETON, AND MANNY MAYOR Departments of Neurology, Pharmacology, and Medicine, University of Miami School of Medicine, Miami, Florida, USA Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada Department of Psychiatry and Human Genetics, McGill University, Montreal, Canada Healing Visions Institute for Addiction Recovery, Ltd., St. Kitts, West Indies Behavior Therapy Treatment Research Center, Johns Hopkins Medical School, Baltimore, Maryland, USA

Annals of the New York Academy of Sciences. 2000 Sep 1;914(1):394-401.

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"This is the worst censorship of science in the history of the world… since the dark ages. It's worse than the Catholic Church banning the telescope in 1616” (David Nutt)