But even after all the reading, writing and discussion, I still had questions with unsatisfactory answers. So I decided to do the one thing that was even better than reading scientific articles: I talked to scientists.
Two scientists were kind enough to grant me interviews: Dr. Deepak Cyril D'Souza, a psychiatrist and researcher at Yale University, and Dr. Steven Laviolette, a neuroscientist at the University of Toronto. Both are experts on the neurobiology of cannabis, cannabinoids and the brain, and both were ideal and engaging interviewees who have my sincere thanks. I posed to them many of the questions that had come up in the discussions, and added a few new ones that came up while I was learning about their research.
Discussion with Dr. D'Souza
Dr. D'Souza conducted the 2005 study that I cited in part 1, in which different doses of THC were injected directly into the bloodstream. I asked him specifically about his report of elevated anxiety rates in his subjects, a finding which would seem to contradict the assumed affect of the main component of cannabis. "We need to be clear that cannabis and THC are not the same thing,…we did not fully appreciate this at the time that we conceived the study" he said, and noted (as commenters have also noted) that there are important differences in dosage and delivery between what he did in his study and what smokers receive. Furthermore, he pointed out that there are other chemicals which contribute to the net effect of smoking, including the presence of the anti-anxiety, anti-psychotic cannabidiol, which we have discussed elsewhere.
I also asked him about the use of the words "psychosis" and "psychotic", and if what cannabis users experienced could be described as a temporary experience as a schizophrenic. He clarified, "Schizophrenia is a psychotic disorder. THC induces psychotic symptoms. I don't believe that any drug can model a complex disorder like schizophrenia. Elevated intravenous levels of THC can cause symptoms that resemble schizophrenia." He referenced this video of a journalist being injected with THC on BBC, for anyone interested.
When I asked about his reports of paranoia and THC, and the commenter response that anyone would feel paranoid in the lab, he noted that in his double-blind study, people became paranoid only in the THC condition, not on the placebo condition. He also noted that, again, the effect was dose-dependent. He did concede that setting does matter a little in these studies. He also cited the large anecdotal links between cannabis use and paranoia. For example in some surveys between 20% and 50% of individuals have reported paranoia, persecutory ideas, and hallucinations while under the influence of cannabis (see Here and Here).
I also asked about specific findings that he had published. In one recent paper, (2012 Neuropsychopharmacology), he described that the symptoms of time overestimation and underproduction in his THC subjects was blunted in people who used 2-3 times a week. From what I've heard from users, the existence of tolerance does not come as a surprise. But he suggested that it was a surprising finding because 2-3 times per week was considered "light use," but that even that usage rate induced noticeable adaptive changes which weren't limited to the effects of how they experience time. Behavioral effects, subjective effects, cognitive effects including effects on memory, hormonal responses and even EEG changes in response to THC were blunted in the 2-3 a week users. On the topic of EEGs, his lab also found that gamma and beta frequency EEG patterns were reduced in weekly cannabis users compared to non-users. What does that mean? It is a bit too early to tell-- he can only speculate.
Discussion with Dr. Laviolette
Dr. Laviolette is a specialist in the effects of the cannabinoid system on "emotional learning", which can mean a lot of things, but in his lab, it refers to reward-seeking behaviors and learning related to fear. He explained, “Cannabinoid transmission has a long and important involvement in our understanding of emotional learning because not only can modulation of cannabinoid receptors (either activation or blockade) regulate the formation and expression of emotional learning and memory, but the endocannabinoid system in general is a potent regulator of neuronal plasticity mechanisms related to learning and memory."
I asked about the lasting effects of high doses of THC. He replied that his lab was focused on the acute effects, noting as an example that cannabinoid receptor activators in the amygdala can "increase the emotional salience of fear memories" and can affect activity in the prefrontal cortex remotely, but that this occurs at higher doses only. His lab is undergoing further research into how higher doses of THC in young rats affects the actions of cannabinoids in adulthood, as a way of addressing "compelling evidence linking exposure to high levels of marijuana during adolescence to an increased risk of developing schizophrenia-related psychoses in young adulthood."
In 2006, Dr. Laviolette published a review demonstrating the links between cannabinoid and dopaminergic systems. This relationship is of interest since dopaminergic systems are historically credited as the neurobiological root of addiction. And yet, addiction seems to be a low risk in cannabis users. "That's a very interesting and complex question," he responded. He pointed out that the role of dopamine isn't restricted to a single "pleasure" signal, and even has a role in modulating aversive behaviors in the prefrontal cortex. "I think we are beginning to realize that dopamine serves more as a general signal for any sort of emotionally 'salient' event, which acts to guide emotional learning and memory formation, be it reward or fear-related." He noted that cannabinoids strongly influence dopaminergic signaling, but that the effects of their influence are still being studied by their lab and others.
On How We Talk About Cannabis
I asked Dr. D'Souza why it was that scientists and doctors (like himself) tended to describe the effects of cannabis and THC in negative terms. His answer was that his view of cannabis use was colored by his surroundings. As a physician in a hospital, he only sees the people with problems, but he is aware that there may be beneficial effects to cannabinoids. In fact Dr. D’Souza’s lab is actively studying potential beneficial effects of cannabinoids including the effects of THC on pain, and on extinction learning.
I asked both men if they thought that government agencies selectively emphasized negative research findings over positive ones. Dr. Laviolette said, "I think considering how far both the U.S. and Canadian Governments have evolved since the days of ‘Reefer Madness’ is generally quite encouraging. Indeed, the fact that it is actually possible to obtain marijuana for medical purposes is a massive leap forward considering the history of cultural hysteria that has surrounded marijuana in both the U.S. and Canada." But he also recognized that there was considerable trepidation by governments concerning marijuana. When I asked Dr. D'Souza specifically about the language of NIDA, he replied that he couldn't speak for the agency, but “I don’t get the sense that NIDA will only fund studies designed to show that marijuana is harmful.”
I asked both men if they ever felt pressure to perform, publish or propose research that cast cannabis in a negative light. Dr. D'Souza was emphatic. "No. Absolutely not." Dr. Laviolette added, "Personally no, I have not experienced any sorts of pressure one way or the other."
On The Future
One idea that was brought up during the article discussions was that cannabis has been around for so long that it's unlikely that we would learn anything new about it now. It turns out that there actually is a lot to learn. Dr. D'Souza pointed out that there were three historical phases of cannabis research. "There are the thousands of years of uncontrolled data. Then, beginning in 1963, [when THC was identified as the active ingredient] to the mid 1970’s, there was an increase in research including controlled studies. Then not much happened for about 15 years because the mechanism of action of THC remained an enigma. Then in 1988, the cannabinoid receptor was discovered." From that point, studies on cannabinoids have increased exponentially.
Dr. Laviolette explained that "the formal identification of the brain's endocannabinoid system is relatively recent. However, the progress over the last few years has been remarkable," citing as an example the increased understanding of not just Cannabinoid Receptor 1 in the brain, but also Cannabinoid Receptor 2. He noted that there is still a great deal of work to be done to discover the anatomical and functional roles of the endocannabinoid system, specifically as they relate to how they modulate synaptic plasticity, and how that modulation translates into changes in behaviors.
Both researchers are excited by the prospects of useful medical knowledge and applications coming out of cannabinoid research. In fact, both of them referenced the potential therapeutic applications of cannabidiol. But they also strongly suggested that there is much more research to be done on cannabis and cannabinoids.
Dr. D'Souza expressed concern because, although he believes that the majority of people who use cannabis may not experience negative effects, the connection between cannabis use and an increased risk of schizophrenia is still being debated. "If there is a link between [cannabis] and schizophrenia, which is a terrible disorder to have, then we should modify the risk factors." He didn't know precisely what determines a higher risk, but that "some are more vulnerable than others." "The potential consequences of a lifelong disorder shouldn't be minimized." He added that the move to legalize cannabis suggests that more people will be using it. And that means "the studies need to continue.”
Taking a step aside, I wanted to make one (absolutely final) comment. An idea that was brought up in the commentary on the articles was that the only relevant debate about cannabis is its legalization, and that any studies on cannabis now are inconsequential to the sociopolitical discussion. Your opinions on this point are your own. But I've learned from this experience that the scientific debates in the study of cannabis, in neuroscience, in immunology, in pharmacology, and in other fields are not done. Not even close. That may not matter to users, or voters, but it should matter somewhere, and not just to the academics.
Dr. Laviolette offered this fitting conclusion: "Those of us in the basic neuroscience community go where our data takes us, both from the clinical and basic research sides of the equations. I think there are extreme positions on both sides of the debate and the best thing to do is to wait on the science. Reliable, solid, peer-reviewed data is the best way to inform public health policy."