Although it may not be obvious during these Trump-rattled times, we’re in the midst of a psychedelic revival. There is more interest than ever before in experimenting with LSD, magic mushrooms, ayahuasca, ketamine, and other psychedelic drugs.
This renaissance is happening without all the fanfare of the day-glo Sixties, when lysergic acid diethylamide (LSD) escaped from the laboratory and assumed the lead role in an improbable Sorcerer’s Apprentice tale. The phrase “stranger than fiction” doesn’t do justice to the real-world trajectory of LSD, a once-secret weapon of the Central Intelligence Agency (CIA) and the U.S. army, which shape-shifted into a potent counterculture catalyst and dazzled the minds of artists, scientists, inventors, healers, and many others.
While LSD never achieved the social popularity of cannabis, the two substances were linked during the social tumult loosely known as “the Sixties.” Almost everyone who tried LSD back in the day also smoked marijuana. These mood-altering drugs were like a one-two punch that wobbled the American psyche. The ensuing backlash was fierce and efforts to integrate cannabis and LSD into the mainstream were frustrated for decades. Under federal law both are still officially Schedule I substances, a category reserved for dangerous drugs with no medical value.
It’s taken a while, but psychedelic advocates are regaining the momentum. To win social acceptance, they’ve adopted the successful strategy that marijuana proponents have pursued – emphasize the medical aspect, produce some solid science, and show that psychedelics can cure deep psychological wounds when administered under the watchful eye of a trained health professional. Today’s psychedelic champions are careful to distance themselves from the memory of 1960s, even as they carry on its legacy. Whereas Sixties radicals celebrated LSD as a chemical capable of subverting the established order, psychedelics are now being promoted as a remedy for traumatized soldiers.
What is LSD good for?
In what way is LSD therapeutic? And how, if at all, does this relate to medical cannabis? To answer these questions, it’s helpful to survey the various groups of people that got involved with LSD before it became illegal in the United States in the mid-1960s. These groups, representing disparate segments of society, all had different ideas about LSD and how it could be used to advance their specific agendas.
The scientific pioneers who began experimenting with LSD in the late 1940s and early 1950s saw it as a powerful instrument for studying how the mind works, a long-awaited chemical key for unlocking the mysteries of brain chemistry and mental illness. A boon for neuroscience, this exciting new research tool gave rise to novel theories about the biochemical basis of schizophrenia and possible remedies for this perplexing malady.
Very early on, LSD was also embraced – albeit secretly – by the CIA as a “potential new agent for unconventional warfare.” This is how LSD was described in once-classified CIA documents in the 1950s. At a time when society at large knew precious little about LSD, American spy chiefs viewed this odorless, colorless, and tasteless compound as the key to revolutionizing the cloak-and-dagger trade, a means of affording U.S. intelligence a decisive advantage over its Cold War rivals.
The U.S. military also had big ideas about LSD. U.S. Army strategists were high on the prospect of deploying LSD as a psychochemical weapon – spray a cloud of “madness gas” over a city and you could incapacitate a large population without killing anyone. Or so they fantasized. LSD raised the possibility of a new kind of battle weapon that would supposedly usher in an era of “war without death.”
By the late 1950s, a growing number of psychiatrists and other physicians were touting LSD as a healing agent that could expedite the process of psychotherapy. LSD had an uncanny ability to make the unconscious conscious, to illuminate long-hidden sources of stress and neurotic behavior by bringing to the surface whatever might be lurking in the depths of the mind. Hence the word “psychedelic,” which literally means “mind manifesting.”
Taking LSD does not guarentee that a person’s consciousness will automatically be “expanded” or that one will neceessarily have a religioius experience or live a spiritual life thereafter. But the overpowering immediacy and experiential density of LSD can be conducive to deep insight and healing. Dr. Albert Hoffman, the Swiss chemist who discovered LSD, described it as “medicine for the soul,” a tool to help us become who we are supposed to be.
During the 1960s, the therapeutic potential of LSD was projected onto a broad social landscape. Acid was trumpeted by Timothy Leary and his counterculture acolytes as a cure-all for a sick society, a species-catalyst capable of catapulting humanity to the next evolutionary level.
This utopian vision seems worlds apart from the covert use of LSD as an espionage weapon, yet both share a common theme. With the benefit of hindsight, we can look back and see that every group that got involved with LSD became very enthusiastic about the grandiose possibilities conjured by the drug. They all viewed it as the key to the big breakthrough. In each case, the encounter with LSD triggered an envisioning of new possibilities. Whether or not these different possibilities would ever be actualized is another matter, but the opening, the awakened sense of potential, was real.
In essence, LSD and other psychedelic drugs are best understood as potentiators of possibility – for good or ill.
Is Cannabis psychedelic?
Magic mushrooms, ayahuasca, peyote, rue, iboga … these vision-inducing flora and fungi are revered as “plant teachers” by native cultures. Cannabis is also a plant teacher, of sorts. But is cannabis a psychedelic drug, a hallucinogen, like magic mushrooms or LSD?
Yes and no. A lot depends on dosage.
LSD is much stronger than smoked cannabis, which doesn’t generally threaten to overwhelm the cognitive mechanism as psychedelic drugs sometimes do. Cannabis and LSD both slow down the passage of time and intensify the present moment. But LSD triggers a departure from normal waking consciousness so preternaturally vivid that a few puffs of weed seem tame by comparison.
Ingesting cannabis can have a far more profound effect than smoking it. Swallowing a chunk of hashish (concentrated cannabis resin) or consuming too much of a cannabis-infused edible can cause intense LSD-like hallucinations.
Dr. Harris Isbell, for many years a CIA contract employee, conducted a scientific study to compare the effects of LSD and tetrahydrocannabinol (THC), the main psychoactive component of cannabis. After giving both compounds to inmates at the federal narcotics hospital in Lexington, Kentucky, Isbell concluded in a 1969 report that a high dose of pure THC could cause hallucinations similar to lysergic acid.
Addiction & depression
LSD, like cannabis, was well regarded among physicians and scientists for its medicinal potential before it became associated with recreational abuse. During the 1950s, high-dose psychedelic therapy showed promise as a treatment for alcoholism. Researchers theorized that an LSD-induced peak experience could lead to a profound, long-lasting change in the way alcoholics and other addicts viewed themselves and the world.
More recently, psilocybin (the magic mushroom compound) has shown favorable results for both smoking cessation and clinical depression. In a 2017 paper in Nature, medical scientists at Imperial College in London reported that patients with treatment-resistant depression experienced significant benefits that persisted after two psilocybin sessions and some psychological counseling. In 2018, the U.S. Food and Drug Administration (FDA) took the unusual step of designating an experimental psilocybin-based compound as a breakthrough treatment for depression in order to fast-track the drug development and review process.
Ayahuasca (the powerful hallucinogen brewed by rainforest shamans in South America) and MDMA (“ecstasy”) have also shown therapeutic benefits in cases of substance abuse and treatment-resistant depression. So has ketamine, an FDA-approved “dissociative anesthetic,” which is administered as an off-label remedy for patients who don’t respond to conventional anti-depressants. Whereas moderate doses of ketamine can banish suicidal thoughts and send one’s darkest moods into remission, high doses can induce a full-blown psychedelic experience.
Fertilizer for the brain
“Special K” acquired a reputation as a party drug many years before scientists discovered that cannabinoid receptors in the brain and the peripheral nervous system mediate ketamine’s painkilling and antidepressant effects. Ketamine also inhibits NMDA, a glutamate receptor, and this triggers the production of a chemical known as “brain-derived neurotrophic factor” (BDNF).
Described as “fertilizer for the brain,” BDNF stimulates the growth of new brain cells, a process referred to as “neurogenesis.” New neurons are continually forming in at least two regions of the adult mammalian brain – the sub-ventricular zone of the lateral ventricle and the sub-granular layer of the hippocampal dentate gyrus. BDNF also stimulates “synaptogenesis,” the formation of new connections between brain cells, which facilitates neuroplasticity, the brain’s ability to adapt to stress and injury and new experiences.
Ketamine, psilocybin and LSD are neurogenic compounds that promote neuroplasticity and new neural connections. Scientists recognize that the anti-depressant effect of psychedelic drugs is contingent upon enhanced neurogenesis. Cannabis, it turns out, is another neurogenic substance that spurs the creation of new brain cells – unlike alcohol exposure, which “disrupts adult neurogenesis” in animal models.
In 2005, researchers at the University of Saskatchewan found that THC increases neurogenesis by activating CB1 cannabinoid receptors in the hippocampus, the locus of short-term, long-term, and spatial memory. And cannabidiol (CBD), a nonintoxicating cannabis component, can reduce anxiety and depression by stimulating neurogenesis in the hippocampus, according to a 2013 Brazilian study in the International Journal of Neuropsychopharmacology.
THC and CBD promote neurogenesis and other health benefits by mimicking and augmenting the activity of endogenous cannabinoid compounds produced in our own brains. These endogenous signaling molecules are part of the endocannabinoid system, which plays a key role in regulating adult neurogenesis and BDNF expression on a cellular level. Endocannabinoids and plant cannabinoids activate the same cannabinoid receptors that densely populate the brain’s neurogenic zones.
5-HT2a: The psychedelic receptor
Scientists are exploring various ways that THC and CBD interact with the serotonin (5-HT) system. CBD, for example, binds to three serotonin receptor subtypes, including 5-HT2a. Aberrant 5-HT2a signaling has been linked to headaches, mood disorders, and hallucinations. The 5-HT2a receptor is also a key mediator of the psychedelic experience. LSD and several other psychedelic compounds bind to 5-HT2a, and this is thought to be responsible for producing many of LSD’s signature effects.
LSD and CBD are both mighty molecules. But CBD is positively un-psychedelic – it’s about the least hallucinogenic substance imaginable. CBD seems to act as a weak 5-HT2a antagonist, which means that it binds to the receptor and partially blocks it. Psychedelics do the opposite – they activate this receptor in a big way. LSD is a super-potent 5-HT2a agonist; it has a much stronger binding affinity for the 5-HT2a receptor than serotonin itself.
THC – unlike LSD and CBD – doesn’t bind directly to 5-HT2a. But THC participates in crosstalk between the endocannabinoid and serotonin systems through a process known as “dimerization.” THC activates cannabinoid receptors – and these receptors can link up and combine with serotonin receptors to form novel signaling complexes called “heterodimers.”
Receptor dimers are a relatively new and controversial area of neuroscience and researchers have barely scratched the surface of understanding these curious protein conjugates. Preclinical studies indicate that conjoined CB1 cannabinoid receptors and 5-HT2a serotonin receptors facilitate the painkilling and the neuroprotective effects of THC, as well as the cognitive deficits caused by THC’s impact on short-term memory. A 2015 report by a team of European scientists observed that CB1/5-HT2a heterodimers are “expressed and functionally active in specific brain areas involved in memory impairment.”
Are these conjoined receptors also implicated in the neurobiological underpinnings of hallucinations that may follow the ingestion of a high dose of THC? Is this why the oral consumption of hashish resin or a well-endowed cannabis edible can trigger kaleidoscopic, LSD-like visions? Several studies suggest that cannabis use promotes 5-HT2a receptor signaling. In 2013, for example, scientists at the University of Kansas found that cannabinoid compounds can upregulate and enhance serotonin 5-HT2a activity in the prefrontal cortex.
Even more intriguing, the molecular pathway that links 5-HT2a and CB1 cannabinoid receptors appears to be a two-way street. In 2006, David Nichols and his team at Purdue University reported that 5-HT2a receptor activation leads to the formation and release of endocannabinoids. The interaction between 5-HT2a receptors and the endocannabinoid system is fundamental to the neurogenic and antidepressant properties of psychedelic drugs.
Microdosing LSD is a lot like CBD
What about microdosing psychedelics? If a high dose of THC can produce effects that are similar to a full-blown psychedelic experience, then microdosing LSD is more akin to taking CBD. According to favorable anecdotal accounts, microdosing magic mushrooms and LSD can help with anxiety, depression, and substance abuse disorders. The same has been said for CBD, which confers therapeutic effects through multiple molecular channels.
One of the ways CBD relieves anxiety is by binding to another serotonin receptor, 5-HT1a. Scientists have identified this receptor as a major target of CBD, more so than 5-HT2a. There’s also a growing body of evidence that CBD has significant anti-addictive potential, a recurring therapeutic attribute of psychedelic compounds. Preclinical research suggests that CBD may have remedial properties for opioid, cocaine, tobacco, and methamphetamine addiction. CBD also protects against neurodegeneration caused by binge-drinking.
A 2017 study in the journal Addiction Biology suggested that CBD can aid in addiction recovery due to its effects on memory. CBD was found to blunt cue-induced cravings that make recovery from addiction very difficult. The importance of forgetting should not be underestimated in mental health, particularly when it involves disrupting an association with a drug-related cue on a visceral level – one of the many gifts of CBD.
Plant cannabinoids like CBD and THC are biphasic compounds, meaning high and low doses convey opposite effects: low doses tend to stimulate, high doses tend to sedate. LSD is also a biphasic compound, as evidenced by the distinctly different effects of macrodosing and microdosing psychedelics – as different as a high dose of THC and a nonintoxicating dose of CBD.
Changing your brain
There’s a saying in neuroscience: “Neurons that fire together, wire together.” Brain habits get stuck. Psychedelics may indeed open the doors of perception. But even more fundamental is how these substances thrust open windows of enhanced neuroplasticity by stimulating the creation of new brain cells and synaptic connections. Science has proven that this is what psychedelics do.
A full-blown LSD experience might last from 8 to 12 hours, but the adaptive changes in the brain triggered by the drug can last much longer. New neural connections may lead to new perspectives. The phrase “high on LSD” implies rising above the ordinary and getting a long-range, overarching view, a big-picture satori – what was once unimagined suddenly becomes saturated with possibility.
LSD has a propensity for catalyzing intensely meaningful moments of vision, those seminal light bulb moments, the explosive epiphanies, which alter mental constructs and transform how we look at things. But integrating those insights and applying them in daily life is easier said than done. Broadening our horizons doesn’t necessarily change our immediate circumstances.
Whether microdosing or chasing the ultimate high, psychedelics are not a quick fix. But they can deliver a neurogenic spark that resets brain circuits in people who are depressed or in a problem-solving rut or who just want some unsupervised awe and wonder. And this reset can resonate well into the future.
Martin A. Lee is the director of Project CBD and the author of several books including Smoke Signals: A Social History of Marijuana – Medical, Recreational and Scientific and Acid Dreams: The Complete Social History of LSD – the CIA, the Sixties and Beyond.
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Sources – A Deep Science bibliography
- Alén F, Mouret A, Viveros MP, Llorente R, Lepousez G, Lledo PM, López-Moreno JA. Converging action of alcohol consumption and cannabinoid receptor activation on adult hippocampal neurogenesis. Int J Neuropsychopharmacol. 2010 Mar;13(2):191-205. doi: 10.1017/S1461145709991118. Epub 2010 Jan 5. PubMed PMID: 20047713.
- Anderson T, Petranker R, Rosenbaum D, Weissman CR, Dinh-Williams LA, Hui K, Hapke E, Farb NAS. Microdosing psychedelics: personality, mental health, and creativity differences in microdosers. Psychopharmacology (Berl). 2019 Feb;236(2):731-740. doi: 10.1007/s00213-018-5106-2. Epub 2019 Jan 2. PubMed PMID: 30604183.
- Barrett FS, Griffiths RR. Classic Hallucinogens and Mystical Experiences: Phenomenology and Neural Correlates. Curr Top Behav Neurosci. 2018;36:393-430. doi: 10.1007/7854_2017_474. Review. PubMed PMID: 28401522.
- Baumeister D, Barnes G, Giaroli G, Tracy D. Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles. Ther Adv Psychopharmacol. 2014 Aug;4(4):156-69. doi: 10.1177/2045125314527985. Review. PubMed PMID: 25083275; PubMed Central PMCID: PMC4104707.
- Bogenschutz MP1, Johnson MW2. Classic hallucinogens in the treatment of addictions. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:250-8. doi: 10.1016/j.pnpbp.2015.03.002. Epub 2015 Mar 14.
- Campos AC, Ortega Z, Palazuelos J, Fogaça MV, Aguiar DC, Díaz-Alonso J, Ortega-Gutiérrez S, Vázquez-Villa H, Moreira FA, Guzmán M, Galve-Roperh I, Guimarães FS. The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system. Int J Neuropsychopharmacol. 2013 Jul;16(6):1407-19. doi: 10.1017/S1461145712001502. Epub 2013 Jan 9. PubMed PMID: 23298518.
- Carhart-Harris RL, Bolstridge M, Day CMJ, Rucker J, Watts R, Erritzoe DE, Kaelen M, Giribaldi B, Bloomfield M, Pilling S, Rickard JA, Forbes B, Feilding A, Taylor D, Curran HV, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl). 2018 Feb;235(2):399-408. doi: 10.1007/s00213-017-4771-x. Epub 2017 Nov 8. PubMed PMID: 29119217; PubMed Central PMCID: PMC5813086.
- Carhart-Harris RL, Goodwin GM. The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology. 2017 Oct;42(11):2105-2113. doi: 10.1038/npp.2017.84. Epub 2017 Apr 26. Review. PubMed PMID: 28443617; PubMed Central PMCID: PMC5603818.
- Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17. PubMed PMID: 27210031.
- Carhart-Harris RL1, Roseman L2,3, Bolstridge M2, Demetriou L4,5, Pannekoek JN2,6, Wall MB2,7,4, Tanner M4, Kaelen M2, McGonigle J4, Murphy K8, Leech R3, Curran HV7, Nutt DJ2C.Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep. 2017 Oct 13;7(1):13187. doi: 10.1038/s41598-017-13282-7.
- de Carvalho CR, Takahashi RN. Cannabidiol disrupts the reconsolidation of contextual drug-associated memories in Wistar rats. Addict Biol. 2017 May;22(3):742-751. doi: 10.1111/adb.12366. Epub 2016 Feb 1. PMID:26833888
- De Gregorio D, Enns JP, Nuñez NA, Posa L, Gobbi G. d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders. Prog Brain Res. 2018;242:69-96. doi: 10.1016/bs.pbr.2018.07.008. Epub 2018 Aug 31. Review. PubMed PMID: 30471683.
- de Oliveira RW, Oliveira CL, Guimarães FS, Campos AC. Cannabinoid signalling in embryonic and adult neurogenesis: possible implications for psychiatric and neurological disorders. Acta Neuropsychiatr. 2019 Feb;31(1):1-16. doi: 10.1017/neu.2018.11. Epub 2018 May 16. PubMed PMID: 29764526.
- Dos Santos RG, Osório FL, Crippa JA, Riba J, Zuardi AW, Hallak JE. Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years.Ther Adv Psychopharmacol. 2016 Jun;6(3):193-213. doi: 10.1177/2045125316638008. Epub 2016 Mar 18. Review. PubMed PMID: 27354908; PubMed Central PMCID: PMC4910400.
- Fadiman J, Korb S. Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. J Psychoactive Drugs. 2019 Mar 29:1-5. doi: 10.1080/02791072.2019.1593561. [Epub ahead of print] PubMed PMID: 30925850.
- Fattore L, Piva A, Zanda MT, Fumagalli G, Chiamulera C. Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine. Psychopharmacology (Berl). 2018 Feb;235(2):433-445. doi: 10.1007/s00213-017-4793-4. Epub 2017 Nov 25. Review. PubMed PMID: 29178010.
- Fernández-Espejo E, Núñez-Domínguez L. Endocannabinoid-mediated synaptic plasticity and substance use disorders. Neurologia. 2019 Mar 8. pii: S0213-4853(19)30010-6. doi: 10.1016/j.nrl.2018.12.004. [Epub ahead of print] Review. English, Spanish. PubMed PMID: 30857785.
- Ferreira RCM, Castor MGM, Piscitelli F, Di Marzo V, Duarte IDG, Romero TRL. The Involvement of the Endocannabinoid System in the Peripheral Antinociceptive Action of Ketamine. J Pain. 2018 May;19(5):487-495. doi: 10.1016/j.jpain.2017.12.002. Epub 2017 Dec 13. PubMed PMID: 29247851.
- Flanagan TW, Nichols CD. Psychedelics as anti-inflammatory agents. Int Rev Psychiatry. 2018 Aug 13:1-13. doi: 10.1080/09540261.2018.1481827. [Epub ahead of print] PubMed PMID: 30102081.
- Fogaça MV, Galve-Roperh I, Guimarães FS, Campos AC. Cannabinoids, Neurogenesis and Antidepressant Drugs: Is there a Link? Curr Neuropharmacol. 2013 May;11(3):263-75. doi: 10.2174/1570159X11311030003. PubMed PMID: 24179463; PubMed Central PMCID: PMC3648779.
- Franklin JM, Carrasco GA. G-protein receptor kinase 5 regulates the cannabinoid receptor 2-induced up-regulation of serotonin 2A receptors. J Biol Chem. 2013 May 31;288(22):15712-24. doi: 10.1074/jbc.M113.454843. Epub 2013 Apr 16. PubMed PMID: 23592773; PubMed Central PMCID: PMC3668730.
- Galindo L, Moreno E, López-Armenta F, Guinart D, Cuenca-Royo A, Izquierdo-Serra M, Xicota L, Fernandez C, Menoyo E, Fernández-Fernández JM, Benítez-King G, Canela EI, Casadó V, Pérez V, de la Torre R, Robledo P. Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells. Mol Neurobiol. 2018 Aug;55(8):6347-6361. doi: 10.1007/s12035-017-0833-7. Epub 2018 Jan 2. PubMed PMID: 29294249.
- Galve-Roperh I, Aguado T, Palazuelos J, Guzmán M. The endocannabinoid system and neurogenesis in health and disease. Neuroscientist. 2007 Apr;13(2):109-14. Review. PubMed PMID: 17404371.
- Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. PubMed PMID: 27909165; PubMed Central PMCID: PMC5367557.
- Howland RH. Antidepressant, Antipsychotic, and Hallucinogen Drugs for the Treatment of Psychiatric Disorders: A Convergence at the Serotonin-2A Receptor. J Psychosoc Nurs Ment Health Serv. 2016 Jul 1;54(7):21-4. doi: 10.3928/02793695-20160616-09. PubMed PMID: 27362381.
- Isbell H, Jasinski DR. A comparison of LSD-25 with (-)-delta-9-trans-tetrahydrocannabinol (THC) and attempted cross tolerance between LSD and THC. Psychopharmacologia. 1969;14(2):115-23. No abstract available. PMID: 5350620
- Jiang W, Zhang Y, Xiao L, Van Cleemput J, Ji SP, Bai G, Zhang X. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest. 2005 Nov;115(11):3104-16. Epub 2005 Oct 13. PubMed PMID: 16224541; PubMed Central PMCID: PMC1253627.
- Johnson MW, Hendricks PS, Barrett FS, Griffiths RR. Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacol Ther. 2018 Dec 4. pii: S0163-7258(18)30215-8. doi: 10.1016/j.pharmthera.2018.11.010. [Epub ahead of print] Review. PubMed PMID: 30521880.
- Khakpai F, Ebrahimi-Ghiri M, Alijanpour S, Zarrindast MR. Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system. Biomed Pharmacother. 2019 Apr;112:108717. doi: 10.1016/j.biopha.2019.108717. Epub 2019 Feb 28. PubMed PMID: 30970516.
- Kvam TM, Stewart LH, Andreassen OA. Psychedelic drugs in the treatment of anxiety, depression and addiction. Tidsskr Nor Laegeforen. 2018 Nov 12;138(18). doi: 10.4045/tidsskr.17.1110. Print 2018 Nov 13. Review. English, Norwegian. PubMed PMID: 30421744.
- López-Giménez JF, González-Maeso J. Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways. Curr Top Behav Neurosci. 2018;36:45-73. doi: 10.1007/7854_2017_478. Review. PubMed PMID: 28677096; PubMed Central PMCID: PMC5756147.
- Madsen MK, Fisher PM, Burmester D, Dyssegaard A, Stenbæk DS, Kristiansen S, Johansen SS, Lehel S, Linnet K, Svarer C, Erritzoe D, Ozenne B, Knudsen GM. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. 2019 Jan 26. doi: 10.1038/s41386-019-0324-9. [Epub ahead of print] Erratum in: Neuropsychopharmacology. 2019 Mar 8;:. PubMed PMID: 30685771.
- Malone TC, Mennenga SE, Guss J, Podrebarac SK, Owens LT, Bossis AP, Belser AB, Agin-Liebes G, Bogenschutz MP, Ross S. Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy. Front Pharmacol. 2018 Apr 3;9:256. doi: 10.3389/fphar.2018.00256. eCollection 2018. PubMed PMID: 29666578; PubMed Central PMCID: PMC5891594.
- Martin DA, Nichols CD. The Effects of Hallucinogens on Gene Expression. Curr Top Behav Neurosci. 2018;36:137-158. doi: 10.1007/7854_2017_479. Review. PubMed PMID: 28677095.
- Mason NL, Mischler E, Uthaug MV, Kuypers KPC. Sub-Acute Effects of Psilocybin on Empathy, Creative Thinking, and Subjective Well-Being. J Psychoactive Drugs. 2019 Feb 26:1-12. doi: 10.1080/02791072.2019.1580804. [Epub ahead of print] PubMed PMID: 30905276.
- Nichols DE. Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD). ACS Chem Neurosci. 2018 Oct 17;9(10):2331-2343. doi: 10.1021/acschemneuro.8b00043. Epub 2018 Mar 1. PubMed PMID: 29461039.
- Nichols DE, Johnson MW, Nichols CD. Psychedelics as Medicines: An Emerging New Paradigm. Clin Pharmacol Ther. 2017 Feb;101(2):209-219. doi: 10.1002/cpt.557. Epub 2016 Dec 26. Review. PubMed PMID: 28019026.
- Pacheco DDF, Romero TRL, Duarte IDG. Ketamine induces central antinociception mediated by endogenous cannabinoids and activation of CB1 receptors. Neurosci Lett. 2019 Apr 23;699:140-144. doi: 10.1016/j.neulet.2019.01.059. Epub 2019 Feb 1. PubMed PMID: 30716423.
- Patra S. Return of the psychedelics: Psilocybin for treatment resistant depression. Asian J Psychiatr. 2016 Dec;24:51-52. doi: 10.1016/j.ajp.2016.08.010. Epub 2016 Aug 23. Review. PubMed PMID: 27931907.
- Prenderville JA, Kelly ÁM, Downer EJ. The role of cannabinoids in adult neurogenesis. Br J Pharmacol. 2015 Aug;172(16):3950-63. doi: 10.1111/bph.13186. Epub 2015 Jun 16. Review. PubMed PMID: 25951750; PubMed Central PMCID: PMC4543605.
- Reiche S, Hermle L, Gutwinski S, Jungaberle H, Gasser P, Majić T. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:1-10. doi: 10.1016/j.pnpbp.2017.09.012. Epub 2017 Sep 22. Review. PubMed PMID: 28947181.
- Rodrigues RS, Lourenço DM, Paulo SL, Mateus JM, Ferreira MF, Mouro FM, Moreira JB, Ribeiro FF, Sebastião AM, Xapelli S. Cannabinoid Actions on Neural Stem Cells: Implications for Pathophysiology. Molecules. 2019 Apr 5;24(7). pii: E1350. doi: 10.3390/molecules24071350. Review.
- Roseman L, Nutt DJ, Carhart-Harris RL. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression. Front Pharmacol. 2018 Jan 17;8:974. doi: 10.3389/fphar.2017.00974. eCollection 2017. PubMed PMID: 29387009; PubMed Central PMCID: PMC5776504.
- Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165-1180. PubMed PMID: 27909164; PubMed Central PMCID: PMC5367551.
- Rucker JJH, Iliff J, Nutt DJ. Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology. 2018 Nov;142:200-218. doi: 10.1016/j.neuropharm.2017.12.040. Epub 2017 Dec 25. Review.
- Seyrek M, Kahraman S, Deveci MS, Yesilyurt O, Dogrul A. Systemic cannabinoids produce CB₁-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT(7) and 5-HT(2A) receptors. Eur J Pharmacol. 2010 Dec 15;649(1-3):183-94. doi: 10.1016/j.ejphar.2010.09.039. Epub 2010 Sep 21. PubMed PMID: 20868676.
- Viñals X, Moreno E, Lanfumey L, Cordomí A, Pastor A, de La Torre R, Gasperini P, Navarro G, Howell LA, Pardo L, Lluís C, Canela EI, McCormick PJ, Maldonado R, Robledo P. Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors. PLoS Biol. 2015 Jul 9;13(7):e1002194. doi: 10.1371/journal.pbio.1002194. eCollection 2015 Jul. PubMed PMID: 26158621; PubMed Central PMCID: PMC4497644.
- Wolf SA, Bick-Sander A, Fabel K, Leal-Galicia P, Tauber S, Ramirez-Rodriguez G, Müller A, Melnik A, Waltinger TP, Ullrich O, Kempermann G. Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Commun Signal. 2010 Jun 17;8:12. doi: 10.1186/1478-811X-8-12. PubMed PMID: 20565726; PubMed Central PMCID: PMC2898685.
High Times cover story by Martin A Lee highlights the breakthrough research on CBD, and how it has revolutionized the story of cannabis medicine.
Data shows that CBD interacts directly with the CB1 cannabinoid receptor in therapeutically relevant ways while modulating THC's psychoactive effects.