After reading psychedelic information theory, I’ve become more and more interested in the molecules behind so-called ‘spiritual’ phenomena occurring in the brain. The fact that DMT, a neurotransmitter which is released during dreaming, evokes the question: Why do we dream? The main hypothesis is that dreaming (and here characterized by both non-REM and REM sleep) somehow processes all subconscious material and emotional content that we have been experiencing on the day of the dream. As of here arises the theories surrounding dream theory and dream analysis (as per e.g. Freudian analysis).
So if DMT is the main molecule released during sleep (along with acetylcholine; a neurotransmitter associated with memory-processes) why is it in plants too? Do plants dream? And if they dream, what do they dream about?
The pineal gland is thoroughly implicated in dreaming and has been characterized as the brain’s Third Eye by e.g. Hinduism. The pineal gland controls the release of melatonin, which is the main hormone released which induces sleep. The pineal gland also stimulates the release of DMT under strong meditative experiences or otherwise transcendental experiences.
Interestingly, the transcendental experiences and the subsequent enlightenment experienced by people who have meditated for several years can be accelerated or achieved by continual use of magic mushrooms.
Psilocybin
Several scientists such as Richard Feynman, Francis Crick, Kary Mullis and others have used psychedelics and other means of altering one’s state of consciousness (Feynman was a fan of sensory deprivation) to look at things from a new perspective.
Psilocybin, the active ingredient in ‘Magic Mushrooms’, or Psilocybe mushrooms has profound effects in people.
A study published in 2011 by Rácz J., et al., in the Journal of Psychoactive drugs, writes: “The autognostic use of psychedelic drugs may be thus hypothesized as a “training situation” that promotes self-enhancement by rehearsing personal coping strategies and by gaining self-knowledge. However, to assess the actual efficiency and the speculated long-term benefits of these deliberately provoked exceptional experiences, further qualitative investigations are needed.”
More interestingly however, are the studies published from John Hopkins University where a controlled set (people) and setting (environment) was used to achieve the best results using psilocybe mushrooms. They called the study: “Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness.”, where 18 healthy adults (avg. age: 46) got to experience a five to eight hour experience with either psilocybin (at different doses) or placebo. All of the participants were interested in spiritual experience and were open to the experience coming their way.
The effects of this study were profound, especially because the participants of the study were asked fourteen months after the experience and asked a number of questions relating to their quality of life, levels of spirituality. Accordingly, 94% of the participants described the experience as one of the most meaningful experiences in their lives, 39% of which said it was the most meaningful.
The effect of the experience didn’t only relate to the individual however, but also had glowing effects on friends, family, co-workers, all of whom reported the participants as less stressed, more calm and happier. As per the abstract: “Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.”
The experience itself is described as being part of a whole, as of relating to a higher state of being, as of seeing the Universe in a new light. Ayahuasca used by the tribes in the Amazonian Colombia have used combination of plants containing DMT (which isn’t orally active) and a monoamine oxidase inhibitor naturally found in Caapi (a plant), which when taken orally (in the form of a drink) allows for a highly transcendental experience. The shamanistic movements believe that only by using these forms of enlightening combinations of being exposed to nature, meditation and of deep insight can revelations of the Self be explored. The reason that some people have bad trips is mostly related to the fact that most people do not like the loss of control that is experienced under the influence of psychedelic drugs. Psychedelic drugs can induce a phenomenon known in parapsychology as the death of one’s ego, or egodeath – as described by the author Eckhart Tolle:
I couldn’t live with myself any longer. And in this a question arose without an answer: who is the ‘I’ that cannot live with the self? What is the self? I felt drawn into a void. I didn’t know at the time that what really happened was the mind-made self, with its heaviness, its problems, that lives between the unsatisfying past and the fearful future, collapsed. It dissolved.
It is reported that the day after this experience he was peaceful and even saw peace in the traffic in the streets of London.
And for the record: I am in no way condoning the use or misuse of psychedelic drugs (as they can have highly detrimental effects in those susceptible, and requires both preparation in terms of set and setting) – magic mushrooms and other psychedelics as e.g. LSD and DMT are tools for enlightenment and not toys.
SSRIs are selective serotonin re-uptake inhibitors, commonly referred to as antidepressants, and they are some of the most widely prescribed pharmaceuticals in the world. One of the first SSRIs and most well known is called Prozac (chemical: fluoxetine) marketed by Eli Lily And Company. Another two well-known SSRIs are Lexapro (chemical: escitalopram) and Zoloft (chemical: sertraline) marketed by Lundbeck and Pfizer. This post wants to take a look at one of the biggest myths that surrounds the use of antidepressants (most commonly SSRIs).
The Placebo Myth
There are an increasing number of people re-iterating the same point about SSRIs over and over again. “They are not much better than placebo”. Let’s actually take a look at the evidence. When people say stuff like that, it is either because they a) don’t know anything about the drug, and have a very negative outlook on pharmaceuticals as whole, and therefore makes grand-assumptions with no evidence, or b) they have read one of the many news articles featured in even highly respected newspapers such as the New York Times, who indirectly refers to a meta-analysis done by the Cochrane group. Moreover journalists love to write about controversial findings, such as any preliminary evidence suggesting a widely prescribed class of drug could be ineffective. That said, meta-analyses look at the plethora of studies available on a specific topic of interest, and use various statistical methods to derive a conclusion as to what the majority of evidence suggests. The meta-analysis (1) by the Cochrane group suggested that SSRIs and TCAs (tetra-cyclic antidepressants) were only minimally (and not clinically significantly) better than placebo in the treatment of mild depression.
Interestingly, this meta-analysis has been criticized wildly by a number of other researchers due to methodological flaws. Several papers have been sent in return. Let’s take a look at some of them and their conclusions.
In the first letter (2) Glassman et al, found that several other studies suggest that it is not only the severity of the depression that predicts the outcome of medication treatment, but also duration of treatment. Several studies are cited showing significant antidepressant effect in dysthymia (a chronic form of mild depression), and another cohort of studies showing significant results in cohorts with mild depression. “The authors’ observation about depression severity is almost certainly correct, but their conclusion concerning antidepressant medication use is not.”
In the second letter (3) Suzuki et al, suggests that there is a bias towards studies with a limited time frame, with approximately 6 weeks, which could compromise the outcome of the subjective rating of depression. This is due to the fact that there is an adaptation period to SSRIs, and depending on the subcategory of depression, some patient may not see immediate improvement, and need more than 6 weeks. This phenomenon is also seen in anxiety disorders treated with antidepressants. Another point the author points out is that the studies referenced do not include remission rates, but merely depression scale. Furthermore this author references another study showing that antidepressants have significant effect in mild-depression. “First, antidepressants may exert their effects earlier in the course of treatment than previously thought. If so, the exclusion of short-term studies (less than 6 weeks) would have significantly minimized the clinical pertinence of their findings that focused on acute phase treatment. Second, patient-level data on antidepressants vs. placebo could have been analyzed in terms of response and remission rates, as well as their maintenance over time (as is exemplified in a study of schizophrenia treatment), instead of pre-post comparison of the mean values alone.”
In the third letter (4) Hicks et al, notes that mild depression only was evaluated in 1 of 6 studies, (with a score in the Hamilton Depression Rating Scale (HDRS) 8-13), and in that one study the HDRS score was not above 14, equivalent to moderate depression. Moreover, the author criticizes the sample sizes because drug-discontinuation occurs in up to 25% patients, and that there is a 3% dropout rate. The question as to whether the patients in the two studies are representative of the general depression population is posed.
In the fourth letter (5) Gøtzche draws attention to a very important observation. The linear fit in the model used in the meta-analysis was poor and that the statistics shouldn’t have been based on the HDRS scores, but rather remission rates, and the meta-analysis’ statistic method may exaggerate the negative results. “The meta-analysis of antidepressants by Mr. Fournier and colleagues is important for clinical practice, but I have 3 reservations. First, although the authors had access to individual patient data, they used last observation carried forward for patients who dropped out. This method of imputation is likely to overestimate the effect of antidepressants.”
In the fifth letter (6) DeRubeis et al, notes that mild depression was only evaluated in 1 of 6 of the studies in the meta-analysis, making the sample size questionable. The author also points out the problem with heterogeneity in the study population.
Besides being quoted multiple studies in the several letters in response to the Cochrane study, here is a large (7) meta-analysis, which shows that SSRIs have shown efficacy in many studies. This meta-analysis showed that antidepressants were significantly more effective than placebo in the treatment of dysthymia.
There is so much evidence in favor of antidepressants, but because a handful of people do not respond favorable to them, they are demonized by a number of people. Conspiracy theories saying that pharmaceuticals are evil and trying to put “hand-cuffs” on people, and steal their money, should really look at the evidence. Depression is a worldwide phenomenon and negatively affects society as a whole. Treatment options shouldn’t be limited for people who need help.
References
1. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010 Jan;303(1):47-53.[cited 2011 Jul 22 ]
2. Glassman AH. Depression severity and effect of antidepressant medications. JAMA 2010 Apr;303(16):1598; author reply 1599.[cited 2011 Jul 22 ]
3. Suzuki T, Uchida H, Nakajima S. Depression severity and effect of antidepressant medications. JAMA 2010 Apr;303(16):1597-1598; author reply 1599.[cited 2011 Jul 22 ]
5. Gøtzsche P. Depression severity and effect of antidepressant medications. JAMA 2010 Apr;303(16):1597; author reply 1599.[cited 2011 Jul 22 ]
6. DeRubeis RJ, Fournier JC, Fawcett J. Depression Severity and Effect of Antidepressant Medications—Reply. JAMA: The Journal of the American Medical Association 2010 Apr;303(16):1599.[cited 2011 Jul 22 ]
You may have heard about it, because ever since its use boomed in colleges and high-schools, it has gained a massive attention from the public media. Not only anecdotes and success stories, but also ethical debates about whether it should be allowed to enhance mental functions through chemical means. The drug I am talking about is of course the notorious Adderall. Some people call it speed for the mind or productivity in a pill, where others — namely ADHD patients — sees it as a way to be able to function in society, overcome personal struggles and and getting on with their lives .
What is Adderall?
Adderall is a FDA approved drug for the treatment of attention-deficit hyperactivity disorder or ADHD, and narcolepsy. Adderall is a sympathomimetic drug, meaning that it increases sympathetic tone, making us more alert, focused, and motivated. Adderall is an amphetamine. It is a combination of several amphetamine salts. It consists of 75% dextroamphetamine and 25% levoamphetamine. The majority of the Adderall consists, as you can see, of dextroamphetamine. Dextroamphetamine is sold under the brand-name Dexedrine in the US, and was first synthesized in 1887. It wasn’t before the 1970s that the drug was turned into a prescription-drug, and was no longer available as an over the counter drug.
It is very important to note that Adderall is a combination of amphetamine salts, and does not refer to the widely abused drugs such as Esctasy (MDMA) and Crystal meth (methamphetamine). Although the drugs are chemical cousins, the difference is both dosage and the chemicals effects in the brain. The media sometimes demonize use of “amphetamine” in general because they do not know the difference between the chemicals. There is a big difference between MDMA, methamphetamine and pure amphetamine. Because of that demonization it is now very difficult to procure a script for Adderall, even as an ADHD patient, which is a terrible shame since they are the most efficacious for the treatment of ADHD. Adderall was created by the drug company Shire Pharmaceuticals, and was available since 1996.
Uses
ADHD
First, what are the effects of mixed amphetamine salts in ADHD individuals? Since it is FDA approved and indicated for the disorder, it would only be natural that Adderall reduced symptoms of ADHD, and that is indeed what the literature is telling us. There are a ton of articles indicating that the efficacy rates of Adderall for the treatment of ADHD and adult ADHD are very, very high, and [1] is an example of treatment of adult ADHD with Adderall, with very high efficacy rates. It reduces symptoms of inattention, impulsiveness and hyperactivity. The Adderall used in the study is one of two forms of Adderall. There is the slow released, or extended release (called XR) and the instant released, or immediate released (called IR). In the study they used the extended release, which is also preferable for full day coverage of ADHD symptoms.
Cognitive Enhancement
What about Adderall and healthy individuals? There are a tons and tons of anecdotal stories about people’s use of Adderall both for the treatment of ADHD as well as for cognitive enhancement in healthy individuals. The problem with such anecdotes, is that they are just that, anecdotes, and do not allow to look at things objectively. But, just for the sake of it, looking at things subjectively, the anecdotes are very positive as to the effects of Adderall on human cognition. Because of many people’s response to Adderall is has became a common smart-drug in intellectually demanding communities such as colleges and universities, where focus is of crucial importance to one’s performance. A post in the New Yorker [2] called The Underground World of Neuroenhancing Drugs also takes a look at several cognitive enhancers, whereas Adderall is one of those drugs. The anecdotes and subjective reports are very promising, from “I went from a C-average student to an A+ student” and “I could focus incessantly on any subject at hand, and I liked it” and many more, makes us believe that perhaps pills can make us smarter. The fact is, though, that they don’t enhance your baseline intelligence, as I suggested in my latest post here. One noteworthy example where amphetamine salts really showed its potential is in the mathematician Paul Erdös, who when his mother died in 1971 started Dexedrine (dextroamphetamine) for the treatment of depression. He became even more productive than before, and is believed to be the most productive mathematician in the history of mathematics, producing over 1525 papers [3].
References
1. Thomas J Spencer et al., “Efficacy and safety of mixed amphetamine salts extended release (Adderall XR) in the management of attention-deficit/hyperactivity disorder in adolescent patients: a 4-week, randomized, double-blind, placebo-controlled, parallel-group study,” Clinical Therapeutics 28, no. 2 (February 2006): 266-279.
2. “The underground world of neuroenhancing drugs : The New Yorker”, n.d., http://www.newyorker.com/reporting/2009/04/27/090427fa_fact_talbot?currentPage=all.
The advances in neuroscience and pharmacology today are so vast that perhaps one day — in the future — we might be able to selectively enhance certain aspects of our intelligence and/or personality.
The past ten years have brought booming attention to “cognition-enhancing” drugs such as Ritalin, Adderall and Provigil, the first two used for attention deficit disorder, and the latter for narcolepsy and excessive daytime sleepiness. The prospect of such drugs were vast. People want drugs that can enhance their ability to focus at information at hand and learn at greater speeds. An ideal pill for a student enrolled in a demanding program, wouldn’t you say?
The thing is, though, cognitive enhancement per se is very, very difficult. A review-article presented in the journal Pharmacology, Biochemistry, and Behavior January [1] this year looks at different aspects of cognitive enhancement and deliberately critiques the current drugs ability to do so.
First, the article tries to draw attention to how we define a cognitive enhancer. In neuroscience several different parts of the brain need to work in harmony before an efficient state is achieved. Does a cognitive enhancer improve all aspects of intelligence, that is, cross-cortical and even cross-hemispheric communication? Looking at the brain as a network of electric potentials, might upping the voltage allow for faster and better transmission of signals?
How do drugs that we — today — denote cognitive enhancers, actually work? This article is a reflection of my take on cognitive enhancers, while also including my personal conjecture in regards to future cognitive enhancers; what is to be expected?
Efficiency vs. Capability?
One question of importance when speaking about cognitive enhancement is the question of whether a proposed pharmacological agent enhances the efficiency or the capabilities of our current mental abilities? In one scenario, a cognitive enhancer may just enhance the efficiency by which we learn, that is, reduce errors and or the time needed to learn the given material. In another scenario, a cognitive enhancer may actually enhance our current mental capabilities, thereby making it easier for us to actually relate to the material. Say we are given a novel to read and analyze, and we wish to really understand it. Enhancing the cross-hemispheric connectivity and turning the activity in our visual cortex up a notch may be just what we need to really, really understand what we are reading. Being able to see the scenes played out in our head, in such vivid detail, that we become it with the book and time simply passes without us even noticing. Is that what cognitive enhancers does? Warp the time-space continuum, and make us completely entrenched in the task at hand? It may be that by enhancing the very specific areas we use for specific tasks, our ability may be significantly enhanced.
Cognitive Enhancers Available Today?
Ritalin, a notorious drug for hyper-kinetic disorder or ADHD, has become a very, very well-known drug because of its purported effects on human cognition. Drugs such as Ritalin or Adderall (another drug used in the treatment of ADHD) are very popular amongst students enrolled in challenging curricular. The idea is simple. A drug that enhances one’s ability to work for extended periods of time, focused at a task at hand, may effectively enhance all aspects of human cognition, right? Well, that is the purported effects, but what does the evidence tell us?
Given the fact that our performance in mental tasks follows an inverted U-curve relationship response between arousal levels and performance, (see my post on this phenomenon here) the fact that a psycho-stimulant , such as Ritalin or Adderall increases our performance shouldn’t be surprising. The surprising thing is, though, that while the active constituent of Ritalin, methylphenidate may enhance our ability to focus on simple tasks it may not be able to enhance our ability to solve problems requiring selective attention. Most striking, however, was that tests showed that methylphenidate didn’t improve learning or IQ-dependent tests such as Raven’s progressive matrices, but merely enhanced arousal for a given task without affecting underlying neurobiological cortical networks underpinning intelligent problem-solving.
Provigil, another potential cognitive enhancer, indicated for treatment of narcolepsy and excessive daytime sleepiness have shown some efficacy in improving sustained attention in healthy individuals, but nothing really conclusive have come up. The literature on modafinil (the active constituent of Provigil) and cognitive enhancement is conflicting. Some studies shows increased performance, whereas others don’t. One reason for such discrepancies is that we all have different neurological milieu, and therefore also react differently to drugs. Moreover, the problem with drugs such as Provigil, Ritalin and Adderall is that we know almost nothing about their exact mechanism of action, and therefore we cannot say anything conclusive.
Limitless, Is This To Be Expected?
A novel by Alan Glynn The Dark Fields, which also examines the aspect of cognitive enhancement, has now been made to a movie Limitless by Neil Burger. It is about a young copywriter, who in his path to become a successful writer, stumbles upon a top-secret drug which gives him godlike mental abilities. His life changes dramatically from barely being able to write a word in his book to finishing it in three days. Not only his ability to learn has been transformed, but his whole identity. He can now do what he wants because he has the energy, power and mental ability to do so. All that from a tiny pill.
The movie is a perfect example of what sort of ethical dilemmas such a drug instills. Being able to accomplish such great feats in such minimal amount of time is what we all wish for; the panacea over all panaceas. I do not believe that there is such a magic pill or panacea pill out there, and I do not believe that there is going to be — for now. But in time, our ability to understand the underpinning of human intellect may evolve and become more advanced that such a drug may become the future. I can’t say how reality will pan out, but one thing is for sure: only our imagination is the limit.
That said, I think we are going to see some pretty awesome results with histamine H3 receptor antagonists along with ampakine glutamergic modulators, showing theoretically promising results for sleep disorders, memory consolidation, spatial-memory, social-recognition, working-memory capacity and attention.
References
Gary Lynch, Linda C Palmer, and Christine M Gall, “The likelihood of cognitive enhancement,” Pharmacology, Biochemistry, and Behavior (January 6, 2011), http://www.ncbi.nlm.nih.gov/pubmed/21215768.
“I am the wisest man alive, for I know one thing, and that is that I know nothing.” – Socrates.
Let us agree that we do not have a unified theory of intelligence, and that it cannot be accurately quantified. Yes, there are tests that test cognitive abilities, but do they accurately portray intelligence? I do not think so.
Some people argue that creativity and intelligence are two independent processes. I have had big discussions with people on the nature of intelligence and creativity. One girl told me that intelligence and creativity are completely independent, and I objected and said that they are actually interdependent entities. Her argument was this: “Take an autistic person. Say, savant, and give him an IQ-test. Maybe he gets 180 on the test because he is pretty damn good at solving puzzles. But if you ask him about philosophical questions, or ask him to explain metaphors, draw analogies or something like that, he’ll fail miserably.” I responded: “First. You assume that intelligence is based on a test. I do not. I believe there are several different parts of intelligence. Second. You use a person on the autistic spectrum as your reference. Not the ideal scenario, I would argue. But you do have a point. If however, we decide to work from the assumption that intelligence is completely synonymous to intelligence quotient.”
This is just one example, but an excellent one of the type. Many people have been limited by what I am going to call the “fixed” mindset. They think: “We are all a subject of our genes. They determine my intelligence. My creativity. My personality. Everything.” On the one hand they are true, but they are leaving something very important out of the equation. Interaction with the environment. We cannot leave that out. They think that if they have been given an IQ test stating they have an IQ of 100, they should base their entire lives on that premise. “Oh shit. I have an IQ of 100. This means, according to the definition, I can only finish high-school, and will do very badly in university.” I want to really stress this part. This is wrong. A fallacy. IQ is an intelligence quotient, it is a test, and it is not a definitive answer on how much “potential” you have in you, despite what other people say. Moving from the “fixed” mindset to the “growth” mindset, we know today, that the brain can change rapidly given the right stimuli. If you haven’t already, I would say that moving from the “fixed” to the “growth” mindset is one of the most important parts of self-improvement.
Creativity Correlated
Going back to the interdependent aspect of creativity and intelligence, the correlation found by Jung et al in 2009 [1] favors my point. Intelligence and creativity are indeed interwoven entities, and you cannot be highly intelligent without also being highly creative. That is, if we base our definitions on the tests available today.
The study by Jung et al examined the link between a neurochemical called N-acetyl-aspartate, a biochemical found in neuronal cell bodies, the second largest concentrated molecule in the brain (the amino acid glutamate has the biggest concentration), and creativity. NAA has been linked to neuronal cellular processes, and other important biochemical processes [2]. The correlation between creativity and the neurochemical was interesting, because the same people had just found a correlation between levels of NAA in the brain and measures of intelligence. It was a study from Jung et al in 2009 [2] in a paper called Intelligence, which found examining 63 individuals with standard measures of intelligence, that higher concentrations of NAA (N-acetyl-aspartate) in the right posterior gray matter region, were correlated with higher scores of performance IQ.
The study by Jung et al was also one of the first showing a correlation between a neurochemical and creative thinking, based on divergent thinking tests. More studies, with bigger sample sizes are warranted.
In conclusion, while the logical fallacy tells us that we cannot say correlation equals causation, the post hoc ergo propter hoc fallacy, the correlation between the two is an important and interesting advance in understanding the neurochemical basis of creativity.
References
Rex E Jung et al., “Biochemical support for the “threshold” theory of creativity: a magnetic resonance spectroscopy study,” The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 29, no. 16 (April 22, 2009): 5319-5325.
Rex E Jung et al., “Imaging intelligence with proton magnetic resonance spectroscopy,” Intelligence 37, no. 2 (March 1, 2009): 192-198.
