OTC Painkillers and Marijuana-Induced Memory Loss

Δ⁹-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

• Rongqing Chen^1, 4, 
• Jian Zhang^1, 4, 
• Ni Fan^1, 4, 
• Zhao-qian Teng^1, 4, 
• Yan Wu^1, 4, 
• Hongwei Yang¹, 
• Ya-ping Tang³, 
• Hao Sun¹, 
• Yunping Song¹, 
• Chu Chen^1, 2, , 

• ¹ Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
• ² Department of Otorhinolaryngology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
• ³ Department of Cell Biology and Anatomy, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA

I just read this pretty interesting study about the use of ibuprofen to counteract some of the negative memory-related effects caused by smoking marijuana. THC (one of the psychoactive chemicals in cannibis) has the side effect of impairing memory by affecting the COX-2 enzyme through the CB1 receptor (the main receptor that cannabinoids from marijuana interact with). Scientists believe that it is through this enzyme that acute side effects with short term memory, as well as chronic effects of memory deficits, arise. These side-effects significantly detriment the use of marijuana as medicine, as many are concerned about the side effects that come with the drug. However, a recent study by Chen et al suggests that the use of ibuprofen, which inhibits the COX-2 enzyme, could block these effects. It is an interesting paper, and although it is inconclusive and needs to be studied more, this could really help make the medical marijuana a safe alternative drug.

Summary:
"Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ⁹-tetrahydrocannabinol (Δ⁹-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ⁹-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ⁹-THC exposures. Ablation of COX-2 also eliminates Δ⁹-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ⁹-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2."

Read the rest here:
http://www.sciencedirect.com/science/article/pii/S0092867413013603#

The Munchies

A well-known aspect of the marijuana experience is the intense food cravings that engulf a man after smoking. Doritos, ice cream, pizza, and many other tasty treats are popular snacks among marijuana users to satisfy the urge to ingest food while intoxicated.

Increased appetite is a very interesting effect of marijuana, which comes about for several reasons. Pharmacologically, marijuana affects appetite mostly through endogenous cannabinoid receptors in our brain. Marijuana contains many cannabinoids (around 66 of its 480 natural components), which interact with the brain in order to produce the marijuana effect (some of these components are psychoactive, while others do not have much of an effect on humans). One of these receptors is the CB1 receptor, which influences are eating behavior. CB1 affects parts of the hypothalamus and hind brain that regulate food intake, increasing the body's appetite. Additionally, cannabinoid receptors can increase appetite through perceptual effects, such as making food seem more appetizing (limbic forebrain) and increasing the pleasure we get from food (in the reward centers of the brain). The perceptual effects make the act of eating while high extremely pleasurable, which  uses the concept of operational conditioning (learning).

Having said this, the lab is well aware of the effects of marijuana on appetite, and thus, eating habits is one of the metrics we use to measure the effects of marijuana use. All of the participants in the lab have a menu from where they can order as much food as they want (for free!). Their appetite seems to increase in the lab setting, and these changes can sometimes be dramatic. Some of the participants gain so much weight during their stay with us, which can be up to 20 pounds in a month in extreme cases! I am not sure if this is an effect of the marijuana or withdrawal, or the effect of a third variable -- being in the lab. Since these people are already heavy marijuana smokers, I would assume this increase in food intake mostly comes from the availability of the food, as well as the boredom they experience while taking part in our study. Either way, I still get jealous of the free supply of munchies these participants always have at their beck and call.

Enlightenment in a Pill: The Role of Psychedelic Drugs in the Search for Truth

Below is an essay I wrote for my Contemporary Civilizations class about how psychedelic drugs fit into various models of philosophy. The paper mostly focuses on the works of the philosophers, but this is the type of academic analysis of drug experience I hope to be able to develop later in my studies!

The Dangers of Drugs!!

In my Drugs and Behaviors class, we watched the documentary, "The Frozen Addict," about an opioid that is used as a form of synthetic heroin, MPPP. This stuff is terrifying, and I feel like the story surrounding it is enough to scare anyone away from doing unknown drugs (please forward this to your children).

MPPP is a synthetic opioid analgesic that was first synthesized by Albert Ziering and John Lee at Hoffman-LaRoche Laboratories in the 1940s. A chemistry graduate student by the name of Barry Kingston took their techniques, altered it to circumvent legal restrictions, and then produced and sold the substance as a synthetic form of heroin. 

Those of you who are unsure about the concept synthetic drugs (often called "designer drugs") may be more familiar with common forms of synthetic marijuana, often labelled as K2 or Spice. These drugs are legal in many states (not New York!), where one can simply buy a pack at a convenience store. Labelled as "natural herbs," these drugs are simply plants sprayed with synthetic chemicals in order to mimic a marijuana high. Our lab is very interested in the use of this drug, and we make sure to ask all of our participants about their experience with this drug. We try to collect demographic data for a side-study about the effects of K2 and Spice. As of  yet, there have not been many scientific studies about the negative effects of these drugs. However, anecdotal evidence tells us that there is no question about the dangers of synthetic marijuana. From paranoia to headaches to seizures, many users have very negative reactions to these drugs. Those who continue to smoke it usually are not able to smoke marijuana (due to drug tests), and believe that the risky high is preferable to the dullness of sobriety. Our hope is that after enough data about this drug is compiled we can encourage people not to waste their time with such synthetics.

Back to the documentary! MPPP gained mild popularity among opioid users, who enjoyed its legal heroin-like effects. However, mistakes in its synthesis lead to its impurity, a substance called MPTP. This substance does not differ so much from the intended product; however, MPTP permanently produces side effects similar to Parkinson's disease symptoms within a couple of hours of using the drug. The severity of these side effects is terrifying! I am filled with such sympathy towards users who, despite engaging in risky drug-taking behaviors, are given such an unforgiving punishment for taking a drug that they thought was relatively harmless. Barry Kingston eventually developed Parkinson's disease-like symptoms from exposure to his impure product, and was arrested on a different drug charge. Justice was served?

Trier Social Stress Test

One of my favorite aspects of research is the Trier Social Stress Test (TSST). This test is designed to measure each participant's response to stressful situations. To simulate a stressful situation, we put on this cruel little mock interview and mental math test. We tell each participant to prepare a five minute speech for their goal job, which can be anything from a computer technician to a cook. The participant is then brought into an intimidating-looking room (pretty much anything that is bright and somewhat empty) to present in front of two researchers that act as potential employers. The researchers must act very stern and serious in order to create a tense situation for the presenter. The directions for the assignment are read quickly and monotonously to the participant, and the timer is set for 5 minutes. The participants usually start off strong, enthusiastically listing all of their qualifications and past experiences. After about 100 seconds, the presenter inevitably loses steam, starting to stutter and grasp for more things to say. If there is a pause, the researcher simply replies, "You still have time, please continue," forcing the participant into an pressured and intense position. The situation is extremely awkward for not only the participants, but also the researchers, who have to try their best to not show sympathy (or laugh at the participant's discomfort). For me, it is also such a pleasure to see the participant squirm under the intense pressure. Cruel, I know, but these situations are very entertaining, and we can all relate to being in a similar situation at some point.

The Pharmacological Odyssey

A bit about why I am interested in the things I do, with some research updates coming shortly...

I am fascinated by the fields of psychology and philosophy, especially regarding the mysterious realm of psychoactive drugs. My curiosity in the subject began in high school, after reading the classic piece of psychedelic literature, The Doors of Perception by Aldous Huxley. The book sketches out Huxley’s reflection on his first mescaline experience, an unexpectedly mind-blowing experience that led him to reconsider his beliefs on the philosophy of the mind. Utilizing insights from aesthetics, perception, ethics, and existentialism, Huxley was able to create a strong philosophical framework of human psychology and perception. What struck me the most about this book was Huxley’s ability to critically evaluate such an abstract and subjective experience and turn it into a lucid and succinct treatise on what drugs reveal about the mind. His success hinted at a hulking abyss of knowledge about our psychology that lay waiting to be revealed through the study of drugs and the mind. I soon dove into other sorts of drug-related literature, from the primitive academic psychology experiments of the 50’s, to the spiritual ravings of the late 60’s, to the modern-day renaissance of medical research.

Scouring through this body of work, I was often disappointed with the pseudo-scientific and overly-spiritual nature of those writing in the field. I understand that spirituality and religion can play a very important role people’s interpretation of drug experiences, but I feel like there are much more profound realizations to be found using the lens of logic and science. I craved more hard facts! More objective evaluations! More critical thinking! The emotions and passions that have plagued the field are hindering the progress we are making in terms of understanding psychedelic drugs through the human mind.

Feeling as if the voice of science and reason are underrepresented in the field of psychoactive drug research, I am inspired to tackle the subject with the critical mindset of philosophy and the sciences. 

On the Blog

Hello!!! I have started this blog to document my semester as a volunteer at the Substance Use Research Center in the NYSPI/Columbia University Medical Center. A bit about my background before I get into the my interests and research – I am a second-year undergraduate at Columbia University, where I hope to get a degree in Neuroscience and Behavior. I am originally from the Bronx, where I was born and raised. Outside of psychology and school, I have a deep passion for music, especially some of the experimental stuff that lies on the fringes of what would even be considered music. As an outlet for my obsession, I program music for WKCR-FM (mostly free jazz/free improvisation, but I also broadcast classical, latin, and regular jazz occasionally), where I am the head of the New Music Department.

About my research: I am stationed at the Marijuana Laboratory, which is part of the Substance Use Research Center in the New York State Psychiatric Institute-Columbia University Medical Center. I usually help out in the Res Lab, which is the part of the laboratory that houses inpatient research volunteers (though our experiments also have an outpatient component). The head researcher in the Res Lab is Dr. Margaret Haney. She is currently investigating the effect of various nicotine relapse medications alone and in combination with nabilone, a synthetic cannabinoid, on marijuana relapse. The volunteers of our study are between 23 and 50 years old and very heavy marijuana and cigarette smokers. The study consists of a 16-day outpatient and 16-day inpatient research session. Throughout this month-long study, we vary the amount of marijuana and cigarettes the subjects are allowed to smoke. To measure the effect of the medications with marijuana and cigarette relapse, we closely monitor their health, mood, and cognitive ability throughout the various stages of the study

That’s a very brief and vague overview of the sort of stuff that we are doing at the lab. The details will become more clear over the semester as I post about the happenings in our research. In the meantime, enjoy this wonderful picture of one of the spaces in our lab!