Psychedelic Drugs: An Overview

13 min readMay 3, 2020

Soon after I opened my medium account for this module, I chanced upon an article on how micro-dosing on psychedelic drugs has impacted the author, Janet L. Chang, who is a RUE scholar from Brown University[1] and a social activist. The article was the first of its kind that I have ever read, I had no idea that there was such a thing called micro-dosing- taking small amounts of drug regularly and anything about psychedelics and how they were different from common drugs, like cocaine? Upon searching up more about psychedelics, I came up with this mind map (Figure 1.1) to broadly categorise drugs according to their nature and effect.

Chang wrote her article on micro-dosing on magic mushrooms, which are mushrooms that have naturally forming chemical compound Psilocybin, responsible for the hallucinogenic response. For biologists who are curious on the science behind psilocybin, it gets converted to psilocin in the body by dephosphorylation, and psilocin being very similar to serotonin (a naturally forming neurotransmitter in our body that regulates many of our bodily functions[2]) binds to the serotonin receptors in the brain[3], stimulating brain activity.

Figure 1.2: Chemical Structures of Psilocybin, Psilocin and Serotonin.[4]

As Chang recounted her year of micro-dosing on magic mushrooms, taking 0.15–0.2g of mushroom root in a sugar cube for 4 days a week, her main findings were that her anxiety decreased, mood and productivity improved. She attributed much of the change to be with her relationship with herself and others. She claimed that she was more self-aware but less self-conscious, which improved her creativity but reduced her anxiety and depression and also made her more empathetic. In essence, micro-dosing made one more sensitive, in both good and bad ways. It caused her emotions to fluctuate more as well, even if she was more positive on most days but she claims the negative experience stems from her pre-existing mental health issues and are not direct side effects of the drug.

The article changed my perspective about drugs by 180 degrees. It seemed very reliable mostly because Chang specified the procedure for her experiment very clearly in a follow-up post[5] and she used clear rubrics to assess herself logically, which gave me confidence that her judgement wasn’t clogged by the influence. Above her numerous scientific citations, I did some research on my own to figure out the scientific feasibility that psychedelics could be empowering beyond their side effects.

In recent times, more people have been looking into psychedelic use for treatment of medical conditions such as depression[6], PTSD and anxiety. In one study, LSD even showed significant beneficial effect in helping alcohol misuse[7]. How does that work?

Drugs, like any stimulants, affect neuroplasticity. What this means is that it promotes rewiring of the brain. The conformation of synapses, grey matter and neurons are constantly changing in the brain, being affected by external stimulus, emotional experiences etc and this is the phenomenon of neuroplasticity. Drugs affect neuroplasticity, but psychedelics are claimed to promote it, making a positive change in the brain by connecting more parts of the brain together. Consider an MRI of a depressed individual compared to someone who is not (Figure 2.1). The clog in multiple part of their brains stops the flow of fluid chemicals in the brain, which reduces their rationality, metabolism and other essential bodily processes that keeps them in a vicious cycle. Now notice the MRI of an individual who consumes a psychedelic drug (Figure 2.2). Essentially the psychedelic fires the brain up and connects parts of the brains that are normally not triggered without the drug stimulant. There are increased number of dendrites sprouting from nerve cells where electrical impulses are passed onto other nerve cells which stimulate brain activity. (Figure 2.3) Though this is a simplified explanation, it makes logical sense that the drug would help the mental health industry in some way.

Figure 2.3: Effects of three psychedelics, DMT, LSD, amphetamines (DOI) and one control (VEH) on neurons in the prefrontal cortex[10]

Most importantly, drug studies have shown that psychedelics, such as LSD are connected to ego-dissolution[11], which is, a “a compromised sense of possessing an integrated and distinct personality or identity.” Positively, what this means is that under LSD, one is more self-aware but less self-conscious. They are potentially more empathetic and better with people, especially with heightened connection to the pre-frontal cortex[12] of the brain that controls our rational and social behaviour. Another study also mentions that ego-dissolution “component also favoured “productive” features of the psychedelic experience and was relatively independent from the emotional valence of the experience.”[13]

Micro-dosing is controlled and the data on it is extremely rare, so I cannot quantitatively reason on the validity of Chang’s claims using that particular data. But data from the National Survey on Drug Use and Health by United States Department of Health and Human Services, Substance Abuse and Mental Health Services Administration and Center for Behavioral Health Statistics and Quality can be a great starting point for me to test out whether psychedelic drug consumption really improves mental health, a proxy for happiness, in people.

Drugs and Happiness- Basic Statistical Analysis

The dataset has 55271 responses for 3148 variables. Working with such a large data, much time is needed to pick the right variables for the analysis and to groom the data well. The aim of this data analysis experiment is to find out whether psychedelics make people happier, so for that, I need 3 groups of candidates- psychedelic users, other drug users and drug-free people. For that, I used the “have you ever taken __(drug)” variables from each category of drugs, including cigarettes and alcohol. Recoding yes with 1 and no with 0, I can group drug free people by adding all their responses to sum to 0. The psychedelic users have no for all other drugs, but yes/no for psychedelics, with at least one yes. All other respondents fall in the other drug user’s category. In the first round of tabulation, where cigarette and alcohol consumers were also negated from the psychedelic’s category, only 13 respondents remained as pure psychedelics users. Of the 13, the K6SCMON values were only available for 2. Hence this was not a feasible method to compare the proxy for happiness as the error rate is very high with such a small sample. So the final tabulation was done with cigarette and alcohol included from the psychedelic’s category, resulting in 69 respondents. This is the breakdown of the types of respondents in the dataset.

The key variable of interest that determines one’s mental health is the K6SCMON variable. According to the code-book, K6SCMON is defined as

“ a score with values ranging from 0 to 24 indicating the level of psychological distress over the past 30 days (past month). This variable is based on data collected from a series of six questions known as the K6, asking adult respondents how frequently they experienced symptoms of psychological distress during the past 30 days. These questions include the following symptoms of distress: feeling nervous (DSTNRV30), feeling hopeless (DSTHOP30), feeling restless or fidgety (DSTRST30), feeling so sad or depressed that nothing could cheer you up (DSTCHR30), feeling that everything was an effort (DSTEFF30), and feeling down on yourself, no good, or worthless (DSTNGD30). For each of the six items listed above, responses of “all of the time” were coded 4, “most of the time” were coded 3, “some of the time” were coded 2, “a little of the time” were coded 1,and “none of the time” and all other responses were coded 0. These assigned values were summed across the six items to calculate a total score for K6SCMON.”

Figure 3.2: Breakdown of K6SCMON values for all drug users

The figure shows the spread of K6SCMON scores against total number of (different types of) drugs consumed. This means the y-axis will be total no. of drugs (which is a column of additional of all the ‘1’s in the different ‘ever consumed drug x?’ columns. the x-axis is K6SCMON scores. On surface level, I could say that those with lower average drug users are happier (as their K6SCMON scores are lower), but that would be flawed as averages can be misleading without comparing the number of cases.

A Status variable was generated from K6SCMON Values (<=12: 1(happy), >12:0(not happy)). The Average Status Score for the different types of drug users are shown in Figure 3.3. The ‘happiest’ are the non-drug users, followed by all drug users. In this sample, the small population of psychedelic users are supposedly the least happy. It is also intuitive that people who are inherently less happy turn to drugs, so the higher happiness need not be due to the absence of drugs, but their initial higher state of happiness.

Running a logit model gives the following results (Figure 3.4):

Figure 3.4: Logit regression generated in R

Status= 2.843874+ (-0.236285)CIGEVER + (0.285239)SNFEVER+ (0.095334)CHEWEVER+ (0.215216)CIGAREVER+ (-0.076881)PIPEVER+ (0.451608)ALCEVER+ (-0.214863)INHEVER + (-0.521900)ANLEVER+ (-0.442269)TRNEVER+ (-0.125846)STMEVER+ (-0.250376)SEDEVER+ (-0.430129)HEREVER + (-0.407004)CRKEVER + (0.166318)COCEVER + (-0.500042)MJEVER +(0.087466)LSD + (-0.136628)PCP + (-0.002757)PEYOTE + (0.455918)MESC + (0.288789)PSILCY + (-0.094773)ECSTASY + (-0.434902)HALNOST

The coefficients of the different drugs are the change in log odds of Status if the drug is consumed. For example, consuming alcohol increases one’s status by exp(0.451608)= 1.5709; a 57% percent increase in Status. Using this interpretation, only Snuff, Cigar, Cocaine, Mescaline and Psilocybin improves one’s Status (and happiness). The negative coefficient on cigarettes, inhalants, pain relievers, tranquilizers, stimulants, sedatives, heroin, crack, marijuana and other hallucinogens implies that they cause a decrease one’s Status. The coefficients on Chew, LSD, PCP, peyote and ecstasy are insignificant at 10% level of significance and hence cannot be interpreted properly. However, insignificance of coefficient on the drug does not imply that the drug does not affect one’s happiness as every drug either positively or negatively affects them anyways. Insignificant coefficients suggest that the drug does not have a linear relationship with happiness (Status). Maybe, the consumption of LSD/PCP/Peyote gives a curve with a plateau- after a saturation point, since our body grows tolerance to it, the drug no longer exponentially increases our happiness. For addictive drugs on the other hand, i would expect a more linear trend since one’s happiness will depend on consumption of the drug, which is why more hard drugs have significant coefficients. Psilocybin and Mescaline seem to be the only psychedelics suggesting a positive linear correlation with happiness, probably due to its nature and low consumption of the drug anyways.

There are still some fundamental issues with the dataset that becomes a barrier from generating any insights from the visualisations. Firstly, the psychedelics population reported from this dataset is very small, and those with K6SCMON values are even lower, hence I cannot draw a pattern between number of drugs consumed and K6SCMON values. I cannot compare this with other drug users or non-users because the population is largely skewed for comparison. Furthermore, logically speaking, the frequency of drug intake should matter more than the number of drugs taken but there are no variables in the survey for me to get that data. The question asked is “have you ever?” which is vague and misleading because ones happiness is not greatly altered by a single trip. There are also a ton of omitted variables that bias these results. For instance, those who had consumed cocaine once in their life might have made it really big in the career, which relates to their higher happiness. There are so many interaction terms with income, age and other economic and social factors that could make the model a lot more valuable.

In future, I would like to try comparing the coefficients of logit as well as breakdown of k6scmon against different years. As this dataset was from 2014, when views of drugs are far different from that of 1994 or 1984, the relating happiness score might also be different (as happiness is after all, a judgment). Comparing over time could give an insight into how societal views on drugs affect the effect of drugs on people. With more research in the field and more available datasets, more analytics could be done on socio-economic impacts of drugs on livelihood.

Pharmaceutical Drugs and Happiness

So, what is the need for psychedelics to help curb mental illness when synthetic, pharmaceutical antidepressants can do the same thing? True enough, the most prominent antidepressants in the market such as Prozac fall under the category of selective serotonin reuptake inhibitors (SSRIs) which has been a class of drugs that have treated more patients with depression than ever before (before 1988, only tricyclic antidepressants (TCAs) existed, which where not very effective and had a long list of side effects)[14]. Although it was much celebrated in the beginning, SSRIs became questionable in their safety and tolerability after its prolonged use.

Like branches in hallucinogens as psychedelics and dissociative, the broad group of medication for mental illnesses are antidepressants and antipsychotics, the latter are neuroleptics that help schizophrenia. Drugs like Risperidone and Clozapine fall under this category. Apart from common side effects of SSRIs & antipsychotics (Sedation, drowsiness, extrapyramidal symptoms, insomnia, fatigue, headache, anxiety, dizziness, drooling, restlessness, increased prolactin, weight gain, increased appetite, vomiting, constipation, upper abdominal pain, nausea, urinary incontinence, tremor, cold symptoms, cough, runny nose, fever)[15] also causes withdrawal effects, sexual problems, weight gain, feeling emotionally numb and addicted[16]. Withdrawal effects refer to a whole set of side effects that occur from stopping the medication such as dizziness, loss of coordination, fatigue, tingling, burning, blurred vision, insomnia, and vivid dreams. More importantly, Harvard Medical School notes that a more important issue is that SSRIs can result in reduced blood clotting capacity because of a decreased concentration of the neurotransmitter serotonin in platelets[17], which increases the chance of internal bleeding.

What is worse is that a large percentage of schizophrenia patients who are not on antipsychotics showed more periods of recovery and better global functioning than those who are on antipsychotics according to this 15 year study[18]- 65% of patients on antipsychotics were psychotic, whereas only 28% of those not on medication were psychotic . In the book “The Myth of the Chemical Cure: A Critique of Psychiatric Drug Treatment” by Dr Joanna Moncrieff, Moncrieff not only highlights the inefficiencies of the drugs in treating mental illnesses and the commercialisation that overlooks it, she also bolds the adverse long term side effects that include brain damage; put together, it triples a person’s chance of dying prematurely[19]. Prof Irving Kirsch from the department of psychology at Hull University and colleagues in the US and Canada believes that it only does not make sense to prescribe these drugs to anyone but the severely depressed patients who have failed all alternative treatments[20].

But there is hope, in the form of psychedelics. Remember what I said about how they promote neuroplasticity? Not only can psychedelics help curb mental illnesses, they might also be able to undo some of the damage[21] that has been done by pharmaceutical drugs. Nature has given us psilocybin, DMT[22] …maybe it is time to put it to good use. Psilocybin is also deemed to be one of the safest drugs to consume by the Global Drug Survey[23].

This is not to say that it is all easy and definitive so we should go ahead and legalise psychedelics. This is far from what we need to do. Back in 1960s, when ketamine was being studied for use, exploitation and chaos shut down the industry completely[24]. There should be legislation to moderate the usage of psychedelics just like tribe leaders regulate consumption through rituals. If psychedelics become medically legal, proper psychedelic clinic within hospitals that specialise in mental health need to be set up. The dosage and the most relevant psychedelic should be administered properly, the place should be conducive and the caregiver- also being the trip sitter- needs to talk the patient out to let go of their grasp on the trip and let it flow by itself so as to prevent bad trips[25]. Alternatively, setting up micro-dose dispensaries will allow those with prescription to purchase micro-doses of psilocybin mushrooms[26]. As of now, legalisation of research efforts can be the biggest, most important step to take. There are limitations to some of the psychedelic studies discussed, especially because it is a sprouting industry with small samples. Author Scott McGreal quotes a limitation on brain-imaging studies that

“Previous research has found that a number of areas of the brain, including the mPFC and the PCC actually show heightened levels of activity when a person is simply at rest and show decreased activity when concentrating attention on various tasks unrelated to thinking about oneself (D’Argembeau et al., 2005; Wicker, et al., 2003)”[27]

Consequently, uncontrolled variables such as the person’s initial state of thought may interfere with current results. More studies need to be done keeping a group of subjects at rest and a group involved in a task while carrying out their study. Thus, advocating research in this field will be the first step to take. Like all pharmaceutical drugs, this one will also take a long time of testing and retesting to be approved in the market (if it is ever going to be)- probably ten-folds longer.

[1] https://www.linkedin.com/in/janetchang/

[2] https://www.medicalnewstoday.com/articles/232248

[3] https://drugscience.org.uk/drug-information/psilocybin/#002165763063146

[4] https://www.researchgate.net/figure/Chemical-structures-of-psilocybin-psilocin-and-its-endogenous-analogue-serotonin_fig2_306049255

[5] https://medium.com/better-humans/the-curious-beginners-guide-to-microdosing-for-work-relationships-and-happiness-7ceff261e9fb

[6] https://www.ncbi.nlm.nih.gov/pubmed/31382100

[7] https://www.ncbi.nlm.nih.gov/pubmed/22406913

[8] https://www.webmd.com/depression/ss/slideshow-depression-overview

[9] https://www.cell.com/current-biology/fulltext/S0960-9822(16)30062-8

[10] https://www.independent.co.uk/news/health/psychedelic-drugs-brain-repair-lsd-depression-anxiety-lsd-dmt-amphetamines-ketamine-a8395511.html

[11] https://www.cell.com/current-biology/fulltext/S0960-9822(16)30062-8

[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082376/