Wrapping Up The Year

The second semester of my work at the lab is coming to a close, and so I feel like a sort of "wrapping up" might be wanted. However, this time point is more of a construction of my academic life and doesn't really affect my experience at the lab so much. The experiments are year-round, and we are in the middle of preparing participants for the next round of an inpatient/outpatient cycle. I'll continue working as usual in the summer (I might take a little bit of a break so that I can live full-time in the library during finals). In the summer, I will be spending a bit more time in the lab, probably around 4-5 days of the week, while balancing a few other jobs around the city (managing a department at WKCR, doing some music research, tutoring, and receptionist job). With all of this extra time, I hope I can take on a more in-depth project at the lab, maybe something that will occupy me for most of the summer. Maybe this can range from something like reorganizing the lab (which seems menial, but is actually really crucial to making everything more efficient and functional around here), to updating the mass of data that needs to be input into our computers. There is also the possibility of lending a hand in some of the neighboring labs, especially those that do a lot of TSSTs (see my post a bit below to learn about the thrilling experience of making participants feel very awkward...for science!). The cocaine lab is also doing a bit of work with rats and fMRIs I believe, which would be a great chance to learn a few more skill sets over the summer. I think I even heard that the lab is a bit more relaxed over the summer in terms of running experimental cycles. This gives the researchers a bit of a break to maintain records and analyze data. I'll do what I can to lend a hand in these things, so I hope this will be a productive and busy summer.

As my academic year comes to a close, the lab keeps running as usual, churning out more data for the researchers to include in their analysis. I loved the opportunity to balance these two worlds, and as my school life constantly changes, I feel like my own experience of the lab changes with it. I learned a ton about neuroscience and drugs over the last year in my classes, and that has drastically changed my understanding of the lab and of the topics that we are dealing with. Next year, I hope my experience in Biology, Physics, and Organic Chemistry can continue to shift my perspective, leading me deeper and deeper into the rabbit hole of drug research.

On Security

One of the most impressive aspects of the lab is the sophisticated system of security. I definitely won't be going too into details, since I'm sure even the vague details that I know are enough to get me into trouble with the lab and the DEA.

However, I'll talk about the general idea of security, and what it means for the research lab of an illegal drug. Marijuana is a schedule I drug, as part of the five schedule system that rates drugs based on their accepted medical use and abuse potential. Obviously many people contest both aspects of this categorization: marijuana has been shown to have very clear medical use, and the abuse potential has been shown to be much lower than previously believed. With the recent spotlight on reviewing the illegality of marijuana (and almost all other drugs of abuse), this will inevitably change in the coming years, a change that will affect the research of these drugs significantly.

However, in the meantime, the research center and the DEA have to work extremely carefully together to make sure that this research is within the bounds of the lawful activity. In order to make an exception for the researchers, the DEA must ensure that the drugs being delivered to the facility are only being used for research. This means absolute measurements on marijuana used, as well as an extremely powerful safe, with multiple levels of security. The center is also subject to random DEA inspections (one of which I have been able to witness). 

Clearly this is a very stressful topic of all of those who work in the lab. We must make sure that we can maintain our privilege of studying an illegal, so all must be done to convince the government that this exception is for research, and research only.

Horizons: Pseudo-Science and Religiosity in the Realm of Drug Research

I wrote this small essay outlining my experience at the Horizons Psychedelic Conference. The Conference was really fun! However, parts of it left me a bit unsatisfied, as I explain in the paper.

            In downtown New York, scientists, philosophers, spiritualists, and curious minds congregated in Judson Memorial Church for the Horizons conference. The Horizons Conference focuses on providing “a forum that examines the role of psychedelics in science, healing, culture, and spirituality.” By setting up a platform for intelligent discussion, the conference organizers aim to help establish psychedelic drugs as a legitimate topic of interest.

            Psychedelic drugs have long been plagued by the stigma of the 1960’s, where hallucinogens fueled the often incoherent spiritual ravings of the free-love era. Long after the burnout of the hippies, LSD and other hallucinogens continue to be disregarded as a trivial recreational drug for those seeking a fun, colorful experience. However, a vocal community of supporters have been advocating for the benefits of psychedelic drugs, especially in the fields of science and medicine. In the 1950’s, before the explosion of recreational use, LSD and psilocybin were frequently researched at major universities. Stanford and Harvard were leaders in the field, and researchers such as Doctors Timothy Leary, Ralph Metzner, and Richard Alpert performed a large body of psychological experiments on these drugs. This research was rigorous but short-lived. After several controversies regarding psychedelic drugs appeared in universities and the media, research was soon defunded, and the government was quick to label these drugs as restricted substances (later as Schedule I substances after the Controlled Substances Act of 1970). However, over the last 20 years, there has been somewhat of a “psychedelic renaissance,” a renewed interest in studying psychedelics in a research setting. Organizations such as the Multidisciplinary Association for Psychedelic Studies (MAPS) have pushed for a widespread acceptance of the potential benefits of psychedelic drugs, which range from substance abuse therapy to treating PTSD. By promoting research, encouraging drug education, and working with government substance regulatory authorities, MAPS hopes to push the field of psychedelics past the stigma of recreational use and into the world of science.

Although I am already interested in the field of psychedelic research, I still maintain a great amount of skepticism when it comes to psychedelics in science. My experience with learning about psychedelic drugs has often been frustrating, since the field is plagued with many pseudo-scientific and mystical interpretations of the drug experience. Although spiritual and mystical writings have a place in their respective fields, this approach is often presented in lieu of scientific fact in order to offer an understanding of these drugs that always falls short of the rigor that is possible in research. I understand that the psychedelic experience can be very emotional and moving, but when these passionate interpretations are presented as fact, the true potential of psychedelic science is disregarded.

Thus, I went into Horizons with skepticism. I had never attended the conference before, and I did not know whether the atmosphere would be rigorous and scientific, or if the talks would be shrouded with mysticism and pseudo-scientific assertions. Additionally, since I am interested in the scientific side of psychedelics – psychology, neuroscience, and chemistry – I hoped that these talks would be valuable sources of information, not simplified and made accessible for the general audience and the media.

However, once the conference began, I was extremely impressed by the intelligent and informative nature of the talks. The first speakers at the conference were Earth and Fire Erowid, the founders of the massive online drug information resource, erowid.org. Although I knew about the website beforehand, I did not know much about the famous founders, the Erowid couple. Prejudicially, I felt like I expected some sort of vague spiritual talk from two people with names such as Earth and Fire. To the contrary, they presented one of the most insightful and conscious talks of the weekend. Their lecture, entitled “State of the Stone 2013: New Drugs, New Laws, and a New Generation Wisdom Cycle,” focused on giving the audience a debriefing of the rapidly evolving drug scene, both in the US and around the world. The Erowids track the trends and developments of the drug landscape, which is constantly changing with advances in the fields of chemistry and communications, as well as law enforcement efforts to keep up. One of the main focuses was on the many new psychoactive drugs that are legally being sold stores across the US. As new drugs are constantly being synthesized and sold in obscure packaging (methoxetamine is one example), law enforcements struggle to learn about and ban the sale of these substances (in 2013 alone, the DEA has identified 80-100 new substances). These drugs are usually untested, and thus, the health effects are widely unknown and potentially dangerous. Additionally, the labels on these drugs are often not correctly, as Erowid had proven with legal synthetic drugs (although the packaging had specifically said the drug did not contain a certain illegal chemicals, the Erowid lab found that the drug was primarily made up of this specific chemical!). Overall, the Erowids proved that they were keenly aware of the complex, shifting drug environment.

Another talk that interested me greatly was the update from the Johns Hopkins University MDMA-assisted tobacco cessation research. This research especially caught my attention because of its adherence to the rigorous standards of experimental psychology. With data obtained from his research, Dr. Garcia-Romero made an argument about the potential benefits of MDMA with authority and precision. The experimental setup consists of 15 otherwise-healthy adults who are addicted to nicotine, have tried to quit, and currently want to quit. The mean age of the smokers was 51 years old, and the mean years smoking was 30 years. The experiment consists of a combination of regular and MDMA-assisted therapy sessions, during which a patient would attempt to stop smoking cigarettes. After the sessions are over, there are several follow-ups with the patients in order to gauge the lasting effect of this research. The first round of this study has shown an incredible 80% success rate in terms smoking secession, with 20% of the patients relapsing into their smoking addiction. Dr. Garcia-Romero expressed his goal to replicate these promising results in phase two of this experiment.

Although these two talks demonstrated the legitimate nature of the conference, the overwhelmingly positive attitudes about psychedelic drugs hinted towards a bias in the presentation of the material. All of the speakers expressed optimism and success in the field of psychedelics, promising that the field would soon blossom. However, none of the presenters displayed skepticism about psychedelic science, whether that is in the effectiveness of the treatments, the potential harm of using the drugs, or the legitimacy of the research. The unchallenged positive attitude at Horizons made the general sentiment of the conference less persuasive, since the solely positive attitude made the general atmosphere seem almost like a pep rally for those who are already convinced of the benefits of the drugs.

Given the state of psychedelics in mainstream science and media, this sort of attitude is understandable. The pioneers of the field know that psychedelic science is still in its infancy, and there is a long road ahead before the subject attains widespread acceptance. Many people have a negative opinion of psychedelics and have not been convinced towards any potential benefits of using psychedelic drugs. These people are already armed to the teeth with arguments and facts that the media has been communicating about the dangers of psychedelic drugs. At this point, it may be safest to promote the subject with upmost optimism, in order to avoid giving the opposition more reasons to be concerned. Thus, solely broadcasting the positive aspects of the field and its research would help inspire people to keep pushing the field forward until the field gets to the point where critical evaluation of the drugs are more valid. From an educational perspective, I am disappointed that this approach was taken. I would have loved to get a better understanding of the totality of psychedelic drug use, which not only includes its benefits, but also its dangers. Before psychedelics can go on towards becoming a legitimate field of science, these scientists must overcome their fear of rejection. By allowing a free dialogue of what the full implications of psychedelic drugs, the field will be taken as legitimately and seriously as a topic of science and medicine.

The Lying Participant

A topic that I have mentioned before is the possibility of participants lying. This is a very important issue that researchers must face when dealing with human subjects, and it can have severe consequences on the results of the study. Through the various interviews, surveys, and self-reports, we often rely on the information given to us by the participants. It is very important to know about the participants' prior behavior in order to guage the effects of our experiment on them. Additionally, we hope that we can trust the participants' reports during the experiment so that we can have subjective information about the experiment. This information is analyzed along all of the other data that we collect in the study in order to fully evaluate the experimental effects.

However, the largest question is: how can we trust our participants? How do we know that the participants aren't lying, that they aren't exaggerating or changing their answers so that they seem like a "better" participant (although the best participant is the honest one)?

We cannot! The simple answer is that scientists just have to take their word for it. Any lies or exaggerations due significantly impact the results of the study, which is unfortunate. However, human self-reports are extremely important in this sort of study, so we must be able to work around potential fallacy. I'll leave it up to the senior researchers to figure out how to make their evaluation flexible enough to account for data that is incorrect.

The Pains of Pills

Here's a little write-up of an article from Nature Neuroscience from my Behavioral Neuroscience class. It's supposed to be in the style of a "pop science" article for the masses, which pretty much meant paraphrasing the more technical stuff into digestible prose. Enjoy!

Taking a Look at Painkillers

New evidence shows that opioids could potentially disturb activity in some of the learning areas of the brain in the long-term

By Gabriel Ibagon

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Engulfed in the depths of pill culture, Americans are in the depths of a love affair with prescription pain killers. Whether these pills are prescribed to help handle physical pain, or whether people abuse them for their euphoric effects, many people take prescription pain killers without much concern for their long term effects. Brady K. Atwood, David A. Kupferschmidt, and David M. Lovinger have just released a study investigating how opioids, a common form of painkillers, may have long-term consequences on the brain, in the hope that this information can better help us deal with problems surrounding opioid use and abuse.

The National Survey on Drug Use and Health estimates that 1.9 million Americans are currently abusing opioids. Experts believe that the increasing trend of painkiller abuse has come about because of the continuously increasing amount of prescriptions handed out by doctors (from about 75.5 to 209.5 million in the last 20 years), as well as the trend of misperceptions of the dangers of these drugs (National Institute of Drug Abuse). Many people may assume that drugs handed out by doctors would be less harmful than other sorts of illicit recreational drugs. However, prescription painkillers carry just as much potential for harm as many other drugs that are misused. Research efforts have been embarked to further understand what exactly happens to your brain when you take these drugs, and how we can then translate this information to the public to inform them about any adverse effects.  Atwood et al. have investigated the effects of opioid abuse on specific aspects of the brain, which may hint us towards the negative effects people may experience after several years of opioid abuse.

Published in Nature Neuroscience under the title, “Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum,” this study reports that opioids caused several connections in the brains of rats to be less efficient in the aftermath of opioid administration. The researchers used oxycodone, a common prescription painkiller, to see how the dorsal striatum in rats is modified – understanding the “plasticity” of the dorsal striatum after drug use. These rats were then killed and had their brains examined to search for neurological changes, which revealed that several of the opioid receptors in the dorsal striatum part of the brain experienced opioid-induced long-term depression (OP-LTD), which means that the synapses connecting to the striatum became less active. The overall effect of these changes are not known, but by looking at similar studies conducted with alcohol- and marijuana-induced disruptions to the dorsal striatum, scientists suspect that this may affect learning (especially helping us establish habits).

Although this may sound like a grim warning to stop taking your pain prescriptions, we should take a moment to consider what the implications of this research study are. The research has only been done on rats, so while these critters do serve as a good model to begin to understand how opioids work on the brain, we can’t necessarily generalize these findings to the human brain. The dosage used for the rats also seemed extraordinarily high; the rats were given 1mg of oxycodone per kg of body weight, where the usual human dose is around 0.2mg per kg of body weight. The rats were also only examined a few hours to a few days after a dose, which would probably show a different result than someone who takes pain medication every day for a few years. Lastly, the authors expressed their uncertainty about the cognitive and behavioral effects that opioids depression on the striatum would cause.

However, these findings are still significant in that they hint us towards the importance of further understanding the long-term effect of opioids on the brain. Not only are the prescription rates of opioid drugs skyrocketing, the abuse of these drugs is also following suit. As we struggle to find ways to prevent people from misusing these drugs in a potentially harmful manner, we must also try to extend our knowledge in order to understand and treat these potentially harmful effects. Furthermore, science can provide people with tools to educate the public about these drugs, to make our society much more informed and responsible when it comes to using substances. With the health of the public in mind, we must urge that science do all it can to understand the intricacies of opioid use.

 

References

Atwood, Brady K., Kupferschmidt, David A., and Lovinger, David M. (2014). Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum. Nature Neuroscience, 17.4. Retrieved from http://www.nature.com/neuro/journal/v17/n4/pdf/nn.3652.pdf.

National Institute on Drug Abuse. (2011). Prescription Drug Abuse: A Research Update from the National Institute on Drug Abuse. Retrieved from  http://www.drugabuse.gov/sites/default/files/prescription_1.pdf.

U.S Department of Health and Human Services. (2012). National Survey on Drug Use and Health: Summary of National Findings [Data file]. Retrieved from http://www.samhsa.gov/data/NSDUH/2012SummNatFindDetTables/NationalFindings/NSDUHresults2012.htm.

What Makes A Bad Participant?

What makes a bad participant?

Over the course of conducting our study, we encounter hundreds of hopeful applicants, and then scores of participants who make it through the screening. However, there is always one, or two, or a few participants in a round of the study who exemplify someone who is difficult to work with in these circumstances.

The worst thing one can do during the outpatient portion of the study is to not show up. During the outpatient segment, participants are commuting to the lab from their homes several times a week. Once the participants are scheduled for outpatients, many things from physical examinations to drug dosages are carefully scheduled. A missed drug dose can put our schedule in jeopardy, or at least cause inconvenience for the researchers when trying to analyze the data. Being late is another big issue; since the day is scheduled very strictly, being late will cause inconvenience in having to reschedule all of the time points.

Learning ability is also another factor. There are quite a few tasks that the participants must do during the study, and while they aren't incredibly complicated, they still take some learning and understanding. We sometimes run into some difficulty with participants who do not have a strong math or literary background, and thus have a hard time completing some of the math battery tasks or understanding some of the surveys. We try our best to get these participants caught up and understanding, but we often run into patients who are simply unable to understand or complete the tasks. If this causes too much of a problem, we would have to let the patients go.

Another issue is attitude. It is almost unavoidable for the participants to be in a terrible mood when they're at the height of their cigarette and marijuana withdrawal. In monitoring the participant's conversations (which we do with obvious cameras and microphones in the social area. This seems to be a fact that they seem to forget, at least judging by some of the things they say...), we often encounter negative attitudes that may be harmful to the study. If one participant is talking about how terrible the study is, it may bring down the overall morale, which in turn may incite participants to stop cooperating. Additionally, sometimes rumors are started between the participants about something we may have said to them (or at least what they think we said to them), which may spread misinformation among the participants, interfering with the study.

Lying about information is another very big issue, an issue that raises some questions about how to go about human clinical trials. That may be a subject for a future post.

Many participants have shown some of these traits in one way or another. I suppose that our job as researchers is to minimize the damage that uncooperative behavior may cause.

On the Dearth of Participants

Too good to be true.

The appeal of marijuana research is undeniable. For marijuana users, the prospect of being paid to smoke their favorite indulgence all day seems almost too good to be true. Interviewing applicants on the phone constantly reaffirms this fact; people are always surprised that they are getting free, legal marijuana, even asking me to repeat that fact over to them as if I what I was saying is almost inconceivable. So, if this seems too good to be true, why does our lab frequently face the struggle to recruit participants for our studies?

During our initial screening process, we get hundreds of responses from callers all over the New York City area. After seeing our ads in the newspaper or on the Internet, many marijuana smokes jump at the opportunity to take part in our study. Those screening weeks are truly some of the most busy weeks at the lab, and all of our staff are huddled over the phone conducting interviews and keeping up with the pace of the mounting pile of applicants.

However, when it comes to accepting participants for our study, the outlook is much more bleak. The participant requirements for our study are quite strict, and many participants are knocked off the first round of screening simply because they are not fit for our study. On the outset, participants have to be in the NYC area, between the ages of 21 and 50, and current marijuana and cigarette smokers. After they pass these preliminary requirements, they also have to be willing to take part in our 32-day study, which consists of a full 16 day inpatient segment. Many people simply do not feel comfortable spending 16 days cut off from the outside world, confined to a small, windowless space (with no Internet! Cruel and unusual!). Furthermore, the requirement to quit smoking cigarettes for three weeks is daunting, and sometimes turns participants off the study completely. Once the participants know what they're getting into, they must then go through a phone interview, where we scrutinize their past drug use, their legal history, and their medical condition. Many participants who get to this stage end up having at least one factor that is outside of our study requirements. 

At the end of it all, our hundreds of applicants dwindle down to just a handful of possible participants. We feel the most comfortable with at least 6-8 applicants for the outpatient segment of the study, so that we can safely count on 4 for the inpatient segment of the study.

The point of this all is that no matter how attractive and in-demand participating in this study is, participants must pass through many many requirements in order to be a fit subject. While we wish we could make the requirements more lenient to allow more participants to participate, science demands that we keep our requirements strict, so that we can best study the question at hand.