Lucy in the Sky: What we know from LSD research

            This article was authored by Eric Barajas and Stacy Shaw as part of the 2018 pre-graduate spotlight week.

            Rampant TV public service announcements throughout the 1970s, 80s, and 90s warned the public of the harmful consequences of drug use. These commercials often showed the frying of an egg or had an actor portray a psychotic break to demonstrate how harmful drugs are to one’s mental health and their brain. Contrary to common belief, that scrambled egg is not your brain on drugs. While it is evident that drugs can be both addictive and destructive to users and their health, our understanding of our brain on drugs— in particular, Lysergic Acid Diethylamide (LSD) – is limited due to the illegality of psychedelic substances and lack of funding. Although the late Francis Crick (discoverer of the double helix), Bill Gates, and the late Steve Jobs would attribute their success to the enlightening experience of Lysergic Acid Diethylamide (LSD) [1], research opportunities to better understand how LSD affects our brain remains extremely limited.

            Like several important human discoveries, LSD was discovered by accident. In the 1930s, researchers were looking for any possible medical uses for the ergot fungus, and in their attempts, scientists isolated a chemical compound and named it lysergic acid [2]. One of these scientists, Albert Hofmann, while trying to develop a stimulant to help the breathing of people with respiratory diseases, synthesized lysergic acid diethylamide. LSD was tested on animals, and when it was concluded that the drug had little promise for medical use, the research was put to a halt [3]. Several years later in 1943, Hofmann returned to studying the compound that he had once synthesized and accidentally contaminated himself with it. It is believed that he absorbed the LSD through the skin of his fingertips as he attempted to produce a crystallized version of it. Hofmann reports,

“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.”[2]

            Intrigued by the experience, Hofmann intentionally took 250 μg of LSD (little did he know that this is actually a very potent dose) and experienced its magnified mind-altering properties once again. Confirming LSD’s powerful effects on humans, Hofmann and his colleagues published their findings. A few years later, scientists discovered the serotonin molecule and realized that LSD not only had a very similarly looking molecular composition to it, but it also competed for many of the same brain sites [3]. This fascinating finding led investigators throughout the mid-1950s and 60s to administer drugs with psychedelic properties, including LSD, to thousands of healthy volunteers and psychiatric patients. During this time, dozens of scientific publications suggested that talk therapy was much more effective with the addition of a psychedelic substance—in particular, research found that previously untreatable patients suffering from obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), eating disorders, anxiety, depression, alcoholism, or heroin dependence were experiencing better success under the administration of LSD and talk therapy than just talk therapy alone [3].

            Although promising examinations of psychedelic substances captivated the research field, the media’s attention on psychedelic substances focused on public reports of emergency room visits, suicides, murders, birth defects, and broken chromosomes. While some of this is considered to be a gross exaggeration of the effects of psychedelic drugs, unsupervised and heavy use of LSD has been shown to cause hallucinogen-persisting perception disorder (HPPD) [4] and induce comas, hyperthermia, and bleeding [5]. In response to the public’s outcry, the U.S. Congress passed the Controlled Substance Act of 1970, which prohibited the use of LSD and other psychedelic substances. With the illegalization of LSD, there were no longer any funds for research, which forced researchers to abandon their experiments.

            Nevertheless, many people continued to use LSD for recreational and therapeutic purposes across the decades and carried out their own “research”. The large collection of anecdotal evidence—“trip reports”—have inspired many tech-workers in Silicon Valley today to micro-dose LSD before going in to work [6]. A typical dose of LSD ranges anywhere from 30 to 100 μg, and these 9 to 5 workers are taking anywhere between 3μg to 10μg or 1.5μg to 4μg.7 A microdose confers a much weaker effect on the body such as producing a mild euphoria, an energy lift, or added insight, so people are not actually “tripping” [6]. That being said, workers do not report experiencing any visual or audible hallucinations and are able to function appropriately. Workers also tend to report experiencing clearer thinking and increased creativity and productivity [6]. But, why is that?

            While LSD research has largely faded out, a recent study renewed interest in the drug by investigating the neural correlates of LSD using modern neuroimaging techniques. In the study, 20 volunteers either received a placebo or an injection of 75 μg of LSD followed by arterial spin labeling (ASL) measures, blood oxygen level-dependent (BOLD) measures, and magnetencephalography (MEG) measure [8]. These neuroimaging techniques allowed researchers to look at what areas of the participants’ brains became activated when on LSD, and how strongly they were activated (See Figure 1). What the researchers found was, unlike their placebo counterparts, those under the influence of LSD showed higher connectivity between networks in the brain involved in vision, attention, movement, and hearing [8].

 

 Figure 1: Differences in activation between participants on placebo and those on LSD. Image from Carhart-Harris and colleagues [8].

Figure 1: Differences in activation between participants on placebo and those on LSD. Image from Carhart-Harris and colleagues [8].

            Findings that LSD may enhance creativity, potentially through the increased connectivity between sensory areas of the brain, parallels the findings of other research studies that have found some connections between sensory processing and creativity. Specifically, some evidence shows that individuals who have what is known as “leaky sensory gating” (i.e., have more difficult inhibiting irrelevant sensory information) are more likely to report creative achievement in their lives [9]. It is thought that perhaps people who naturally process more sensory information (whether relevant or not) are able to incorporate more stimuli from their environment, which increases their ability to make remote connections between that information.9 The idea is that this, in effect, leads to creativity. Considering this, LSD research results showing increased sensory systems paired with anecdotes’ from “micro-dosers” that LSD gets them to overcome restrictive thinking suggest that LSD may somehow invoke a sort of leaky sensory gating. However, this hypothesis has yet to be tested.

            Interestingly, the idea of LSD’s involvement in decomposing restricted thinking has been posed in other studies relating to treatment of anxiety and addiction. In another study, 10 volunteers with life-threatening diseases participated in LSD psychotherapy for a period of 12 months, and after the year-long commitment, they were tested for anxiety and lasting psychological changes via a State-Trait Anxiety Inventory (STAI) and a semi-structured interview, 10 Participants reported cathartic and insightful experiences such as the restructuring of their emotional trust, situational understanding, habits, and world view, which were associated with a 77.8% reduction in anxiety and a 66.7% increase in quality of life [10]. In regards to addiction, investigators performed a meta-analysis (an analysis that looks at the effects from many different studies) of randomized controlled trials to assess the clinical efficacy of LSD in treating alcoholism. The meta-analysis consisted of six studies which included a total of 536 participants, and showed evidence that a single dose of LSD, when combined with alcohol treatment programs, decreased alcohol misuse at a faster rate than alcohol treatment programs alone [11]. In both cases, it is believed that LSD breaks down restricted thinking and supports individuals in self-actualizing and overcoming their afflictions. In a supervised therapeutic setting, it seems that LSD administration can be a productive implementation and generate enduring benefits, but much further and more elaborate research is needed to confirm this.

            Although there has been a long hiatus in the research of psychedelic substances, there is a lot of promise to come in the subsequent years. Researchers at the Beckley Foundation have recently begun to study LSD and found its involvement in dynamical repertoire re-organizatio [12], semantic activation[13], personality change[14], default-mode network [15], increased global functional connectivity[16], and increased suggestibility [17]. The Beckley Foundation also expects to commence the world’s first LSD-micro-dosing study examining its effects on mood, cognitive functions, creativity, and general wellbeing. Ultimately, the focus of this kind of investigative work shows a lot of potential for learning more about the brain and mind and how these altered states of mind brought upon by these psychedelic substances may be used as tools for mental, emotional, and personal growth.

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Eric is currently a UCLA psychology undergraduate student with research interests in education (e.g., the privatization of education, the convergence of play and learning, individualization of education) and clinical psychology (psychedelic substance psychotherapy as treatment for mental disorders or mental, emotional, and personal growth). Eric has committed the next two years to teaching special education in LA as a Teach for America corps member. His motivation to become a teacher primarily stems from his observation that many students throughout K-12 are not being reached, especially in low-SES communities, and from his conversations with students within his own community, which have reported their experiences on his podcast, the Blatantly Honest Podcast. The goal of the podcast is to provide a space for people of all backgrounds and identities to express very true life stories concerning serious topics, hoping that listeners can relate to or learn from these personal accounts

 

Citations

1.     Love, Dylan. “Meet the Science And Tech Geniuses Who Got High And Solved Amazing      Problems.” Business Insider. August 22. 2013. https://www.businessinsider.com.au/scientists-and-geniuses-who-used-drugs-2013-8#francis-crick-lsd-1

2.     Petechuk, David. LSD. Farmington Hills, MI: Lucent Books, 2005.

3.     Strassman, Rick. DMT: The Spirit Molecule. Rochester, VT: Park Street Press, 2001.

4.     Hermle, Leo, Melanie Simon, Martin Ruchsow, and Martin Geppert. “Hallucinogen-persisting Perception Disorder.” Therapeutic Advances in Psychopharmacology 2, no.5 (2012): 199-205. Doi:10.1177/2045125312451270.

5.     Klock, John C., Udo Boerner, and Charles E. Becker. “Coma, Hyperthermia, and Bleeding     Associated with Massive LSD Overdose a Report of Eight Cases.” Clinical Toxicology 8,   no.2 (1975): 191-203. Doi:10.3109/1556357508988063.

6.     Solon, Olivia. “Meet the Silicon Valley-ites Taking Tiny Hits of LSD to Boost Performance.” WIRED. August 11, 2017. https://www.wired.co.uk/article/lsd-microdosing-drugs-silicon-valley.

7.     Laing, Richard. Hallucinogens: A Forensic Drug Handbook. Amsterdam: Acad. Press, 2003.

8.     Carhart-Harris, Robin & Muthukumaraswamy, Suresh & Roseman, Leor & Kaelen, Mendel   & Droog, Wouter & Murphy, Kevin & Tagliazucchi, Enzo & Schenberg, Eduardo & Nest, Timothy & Orban, Csaba & Leech, Robert & Williams, Luke & M. Williams, Tim & Bolstridge, Mark & Sessa, Ben & McGonigle, John & I. Sereno, Martin & Nichols, David & Hellyer, Peter & Nutt, David. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences. 113(17). 201518377. Doi:10.1073/pnas.1518377113.

9.     Zabelina, Darya L., Daniel O’Leary, Narun Pornpattanangkul, Robin Nusslock, and Mark      Beeman. “Creativity and Sensory Gating Indexed by the P50: Selective versus Leaky Sensory Gating in Divergent Thinkers and Creative Achievers.” Neuropsychologia 69 (2015): 77-84. Doi:10.1016/j.neuropsychologia.2015.01.034.

10.  Gasser, Peter, Katharina Kirchner, and Torsten Passie. “LSD-assisted Psychotherapy for        Anxiety Associated with a Life-threatening Disease: A Qualitative Study of Acute and          Sustained Subjective Effects.” Journal of Psychopharmacology 29, no.1 (2014): 57-68.       Doi:10.1177/0269881114555249.

11.  Krebs, Teri S., and Pål-Ørjan Johansen. “Lysergic Acid Diethylamide (LSD) for Alcoholism: Meta-analysis of Randomized Controlled Trials.” Journal of Psychopharmacology 26,       no. 7 (2012): 994-1002. Doi:10.1177/0269881112439253.

12.  Atasoy, Selen, Leor Roseman, Mendel Kaelen, Morten L. Kringelbach, Gustavo Deco, and    Robin L. Carhart-Harris. “Connectome-harmonic Decomposition of Human Brain   Activity Reveals Dynamical Repertoire Re-organization under LSD.” Scientific Reports   7, no.1 (2017). Doi:10.1038/s41598-017-17546-0.

13.  Family, Neiloufar, David Vinson, Gabriella Vigiliocco, Mendel Kaelen, Mark Bolstridge, David J. Nutt, and Robin L. Carhart-Harris. “Semantic Activation in LSD: Evidence from Picture Naming.” Language, Cognition, and Neuroscience 31, no. 10 (2016): 1320-1327.       Doi:10.1080/23273798.2016.1217030.

14.  Lebedev, A.V., M. Kaelen, M. Lӧvdén, J. Nilsson, A. Feilding, D.J. Nutt, and R.L. Carhart-   Harris. “LSD-induced Entropic Brain Activity Predicts Subsequent Personality Change.” Human Brain Mapping 37, no. 9 (2016): 3203-3213. Doi:10.1002/hbm.23234.

15.  Speth, Jana, Clemens Speth, Mendel Kaelen, Astrid M. Schloerscheidt, Amanda Feilding,      David J. Nutt, and Robin L. Carhart-Harris. “Decreased Mental Time Travel to the past         Correlates with Default-mode Network Disintegration under Lysergic Acid Diethylamide.” Journal of Psychopharmacology 30, no.4 (2016): 344-353. Doi:10.1177/0269881116628430.

16.  Tagliazucchi, Enzo, Leor Roseman, Mendel Kaelen, Csaba Orban, Suresh D. Muthukumaraswamy, Kevin Murphy, Helmut Laufs, Robert Leech, John McGonigle, Nicolas Crossley, Edward Bullmore, Tim Williams, Mark Bolstridge, Amanda Feilding,   David J. Nutt, and Robin Carhart-Harris. “Increased Global Functional Connectivity Correlates with LSD-induced Ego Dissolution.” Current Biology 26, no.8 (2016): 1043-1050. Doi:10.1016/j.cub.2016.02.010.

17.  Carhart-Harris, R. L., M. Kaelen, M. G. Whalley, M. Bolstridge, A. Feilding, and D. J. Nutt. “LSD Enhances Suggestibility in Healthy Volunteers.” Psychopharmacology 232, no.4  (2014): 785-94. Doi:10.1007/s00213-014-3714-z.