Hello. I'm currently a second year BSc Chemistry student in London, on the way to specialising in organic chemistry. I've decided that I absolutely want to go into the field of pharmaceuticals, specifically psychopharmacology (Hamilton Morris may or may not have played a role in my interest in chemistry). However, I am a little concerned with the potential lack of routes for me to take. Due to Chemistry's status as a physical science, a lot of the masters programs offered which seem closest to psychopharmacology are not an option to me. The closest I can get is a few programs in general drug discovery and development. Does psychopharmacology as a field require university level biological knowledge? I have not studied biology since secondary school, and the modules offered at my university that cover synaptic/receptor research and research on the CNS are only available to people from a life science background. Basically, am I a little screwed or is this still achievable for me?

Immunotherapy and Cannabis: A Harmful Drug Interaction or Reefer Madness?

Prior observational research, cited in clinical practice guidelines, found marijuana decreases the efficacy of nivolumab. Reanalysis found that <5% of their statistics could be verified. There were errors in calculating percentages too!

Summary

Two Israeli studies about medical marijuana potentially interfering with immunotherapies like nivolumab for cancer treatment have received substantial attention. However, there have been anonymous but detailed concerns about these reports on PubPeer. This team attempted to verify the data analysis and statistics of these two reports and the published correction. Many findings, including some that could impact the statistical conclusions, could not be verified. Of 22 statistical in the prospective report, 4 could not be repeated using the same statistics or with the provided N. The p-value on 17 corresponded with that of a different statistical test than was listed in the methods. Re-analysis also identified some previously unreported significant differences (e.g., age) between cannabis users and non-users at baseline. Further study of the safety of immunotherapy and cannabis combination may be warranted using patient groups that have been matched on key demographic and medical variables.

Abstract

A retrospective (N = 140) and a prospective (N = 102) observational Israeli study by Bar-Sela and colleagues about cannabis potentially adversely impacting the response to immunotherapy have together been cited 202 times, including by clinical practice guidelines. There have also been concerns on PubPeer outlining irregularities and unverifiable information in their statistics and numerous errors in calculating percentages. This reanalysis attempted to verify the data analysis while including non-parametric statistics. The corrected prospective report contained 22 p-values, but only one (4.5%) could be verified despite the authors being transparent about the N and statistics employed. Cannabis users were significantly (p < 0.0025) younger than non-users, but this was not reported in the retrospective report. There were also errors in percentage calculations (e.g., 13/34 reported as 22.0% instead of 38.2%). Overall, these observational investigations, and especially the prospective, appear to contain gross inaccuracies which could impact the statistical decisions (i.e., significant findings reported as non-significant or vice-versa). Although it is mechanistically plausible that cannabis could have immunosuppressive effects which inhibit the response to immunotherapy, these two reports should be viewed cautiously. Larger prospective studies of this purported drug interaction that account for potential confounds (e.g., greater nicotine smoking among cannabis users) may be warranted.

Overall, the two prior studies, and especially the prospective one, were riddled with errors.

Thoughts?

Here's the link to the free full-text too:

https://www.mdpi.com/2072-6694/16/7/1245

What happens if someone is deprescribed something like risperidone, but is left on an SNRI like duloxetine simulatneously?

I'm not finding very many papers on antipsychotic withdrawal, and even less (like zero) on what happens if someone remains on an SNRI while undergoing withdrawal, so any links would be appreciated if you have them.

hey guys, hope this is a good place to ask.

I'm writing a review on schizophrenia for my assignment, and I came across something that I had missed some time ago. Atypical antipsychotics act as inhibitors on the excitatory 5-HT2a, but agonists on autoinhibitory 5-HT1a. How does this work to neutralise negative symptoms? Depression is generally regarded to be caused by reduced serotonin signalling, hence SSRIs to increase 5-HT in the synapse to keep signalling. How come in this case inhibition of serotonergic signalling reduces depressive symptoms? I just can't find papers that properly explain this mechanistically.

Thank you for anyone answering!

Hi, wondering if anyone has examples of oral depot (a drug being used less frequently than once daily when "normal" dosing is once daily or more frequent) regimens for psych drugs.

I am aware of the now discontinued version of Prozac weekly, whereby 90mg weekly was equivalent to 20mg daily dose. I've also heard whisperings of aripiprazole being used 3 times weekly but am curious what else might be out there. Thanks in advance!

As psychiatry resident I'm approaching a very variegated population: an interesting case of woman in a moderate depressive episode but also affected by primary hyperaldosteronism made me wondering which drug could I administrate her without make her suffering excessive electrolytes unbalancing and/or blood pressure. Any suggestions to go over a classic SSRI/mood stabilizer approach? Thanks for any idea will come ☺️

Corydalis seems to impact the opioid receptors without creating addiction related to dopamine. This study seems to indicate that most of the alkaloids in it interact with opioid receptors and are affected by the administration of narcan. Thoughts on the validity of whether it constitutes as an opioid or not?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704877/

I love learning about medications related to mental health. I don’t know why but I am just not interested in regular pharmacology the way I am with psychopharmacology. I am about to finish a bachelors degree in general studies and am trying to think of career paths. I know my bachelors degree isn’t that useful but I’m thinking about pursuing a masters program in something more specific. I really do not want to do more than a masters or go into med school. I think I would like working in a clinical setting. Are there any job ideas that could work given all of this?

I know that stimulants work via reuptake of dopamine, so are the cognitive enhancing effects due to dopamine binding to receptor subtypes other than D1 and D2?

Forgive my bad knowledge of neuroanatomy, but are other subtypes also expressed as abundantly in areas of the basal ganglia and frontal lobes?

Does 5ht2a antagonism have anything to do with this?

I know plenty of people with commorbid mood disorders/ personality-disorders and ADHD that take stimulants and antipsychotics effectively.

I'd appreciate any insight, thanks in advance.

This question has been on my mind for a while, but I haven't yet found the answers I'm looking for. I work a lot with both direct and indirect sympathomimetics, as well as anticholinergic drugs (in intensive care and anesthesia). It is well known that directly acting sympathomimetics have dose-dependent effects on various receptors, like adrenaline, for example. I am aware that ephedrine, especially in subtherapeutic doses, can have paradoxical effects due to compensatory counter-regulation, although this is individual. It's known with atropine (an anticholinergic) – half an ampoule can make a patient who is already bradycardic in an emergency even more bradycardic.

On ADxS.org, in the dosing guide, it is recommended to start with a significantly smaller dose than the approved initial dose of Vyvanse – an initial dose of 5 mg (or 10 mg) and increase by 5 mg every 5-7 days.

https://www.adxs.org/en/page/232/medication-dosage-for-adhd#content-1241-elvanse-lisdexamfetamine

However, I keep reading here that especially the very low doses of Elvanse can lead to unpleasant effects - it was the same for me. That's why I'm increasingly skeptical of the justification that you can't go wrong with particularly small doses. I would like to understand it better - maybe someone here has more expertise in this area than I do?

Is there a pharmacological explanation for why a very small dosage of Vyvanse can cause unpleasant side effects, which one does not have with a higher dose?

Does anybody know anything about liverwort, specifically radula marginata/perrottetii, as they contain a chemical called perrottetinene wich is almost identical to THC and is the only other plant species known to produce a psychoactive cannabinoid that binds to the cb1 receptors. However there is almost no information about this whatsoever on the internet even though this chemical has been discovered almost 30 years ago, yet somehow slipped by unnoticed. I can’t find any sources or reports on its effects or where to obtain live plants but as far as I can tell it’s like THC but less psychoactive and potentially more medicinal in that it is a better anti inflammatory in the brain and body as well as having less negative side effects. I’m very interested in cultivating and trying this rare and novel psychoactive but have no way to do so atm. I have found only a single reliable source for a live plant of (radula complanata) Wich is not exactly what I’m looking for but might still contain perrottetinene, however nobody has ever tested to see if this is true and only maybe two or three of hundreds of radula species have been shown to have perrottetinene due to lack of research.

Hi! I read about Prozac's blockage of 5HT2C serotonin receptors. I wonder if it is enough to make it stimulating by indirectly increasing dopamine and norepinephrine and if, therefore, it might be recommended for depression with lack of energy and excessive tiredness.

Thanks!

Hello! I am trying to find information specifically on the effects of combined alcohol and stimulant* use, specifically concerta (methylphenidate ER).

*ideally I want information about individuals taking stimulants as prescribed, but other info is also useful.

Some specific questions I have:

• How does alcohol use impact the effects of concerta? / Can alcohol use inhibit the (therapeutic) effects of concerta? /
• If yes, is this inhibition temporary or can it have long term consequences?
• What are the long term vs short term effects of combined use?
• Can alcohol increase tolerance of concerta? (again, would be great if there’s information on people taking concerta as prescribed)

Anything helps, thank you!

Hello,

Ive recently read multiple studies showing that the combination of psychotherapy and psychotropic medication is more effective than either one is alone. Is there a specific type of psychotherapy that especially compliments psychotropic medication? I know that historically, psychoanalysis/psychoanalytic therapy has gone hand in hand with psychopharmacology in the field of psychiatry. Does it matter at all?

A search of this subreddit shows that there has been no discussion of this relatively new ADHD medication. What are your opinions? Have you have clinical experience with it?

Is it essential for 5-HT activating small molecules to cross the BBB? Considering there are 5-HT receptors located throughout the body in places other than the brain, is crossing the BBB necessary for their MOA? Is activating 5-HT receptors within the brain responsible for the more well-known psychedelic effects?

Suppose a 5-HT regulating molecule were to be modified so that it could not pass the BBB yet retain its 5-HT receptor affinity. Could this eliminate certain psychedelic/hallucinogenic effects while retaining neuroplasticity, anti-inflammatory, etc. effects? If this is the case how do we remove BBB permeability yet retain 5-HT affinity?

Hi, hopefully this should be a good sub to ask this in. I currently have a BSc in Compsci which I doubt I can use to get a postgrad degree in something like psychopharmacology or drug discovery so I've been considering a second degree in either chemistry or biochem and just wanted to check here to see if anyone has any perspective on whether it matters much between the two with the intent of going into these postgrad studies. Unfortunately my nearby uni doesn't offer a degree in medicinal chemistry cause I'm sure then that would be the clear choice.
thanks!

Hi there-

Bit of background - did an undergrad degree in psychology, realizing in my senior year that I actually did have an interest in research and not purely clinical practice. Currently in a master's program in applied clinical neuropsychology, and very unsure what path to take from here.

I still strongly desire to go into clinical practice, but I have taken a keen interest in psychopharmacology. The question is, do I pursue Psychiatry, allowing me to practice therapy as well as prescribe and research psychopharmacology? While I could certainly see myself strongly enjoying prescribing/med management, I think the research is slightly more important to me - so I am also considering non-medical routes. Would a clinical psych phd even allow me to perform psychopharm. research as well as therapy?

Any advice welcome -

Thank you!

I understand this is a loaded question. The example I am most interested with is phenethylamines such as 2C-B or MDMA vs bupropion. It seems each of these molecules have large moieties added to the phenethylamine skeleton. Just looking at the structures you would assume they share some characteristics, yet bupropion seems completely different. What specifically about the bupropion molecule makes it non psychoactive (yet pharmacologically relevant)?

Did you know any free software that may help you identyfy any specific ligand as agonist/antagonist of some receptor? AutoDock and similar programs seems to be pretty useless, because it only visualises the way that ligand bind to receptor, but not it action.

I am a psych nurse practitioner student and feel as though my programs psychopharmacology course was lacking to say the least. We used clinical psychopharmacology by ghaemi which was a fantastic book that I plan to review in the future. I also have stahls prescriber guide as a resource for my clinical practice. However I would love recommendations for other resources to further my learning and ensure that I am a competent prescriber. Thank you in advance for your recommendations!

For example, trazodone is 5-HT1A partial agonist. But does it partially activate 5-HT1A presynaptic receptors (autoreceptors) or the postsynaptic 5-HT1A receptors?

Also I know that 5-HT1A autoreceptors are able to downregulate but what about the postsynaptic receptors? Do they also downregulate?

Sorry for bad english.

I'm a bit confused regarding the definition of central stimulants. Why isn't Atomoxetine included in CS, for example?

I recently came across a tragic case where a young person had injected heroine, some variant of benzodiazepine and amphetamine. The patient is presumed to have died from the effects, but it is not thought that she had a suicidal intent. Is it possible that amphetamine could counteract some of the effects of the depressants?

Hey y’all! I’m an incoming 4th year applied mathematics undergraduate. I haven’t really been following the right things in college, and I finally I want to pursue my passion of psychopharmacology research. My plan as of now is to take neuroscience courses in my 4th year and apply for a PHD program in neuroscience. I’m curious if anyone has any suggestions for how I can best follow this passion in my current situation. Whether that’s pursuing different PHD programs or some type of post-bac programs, any advice would be awesome.

Bupropion has been identified as a medication which can cause drug-induced tremor. Having a hard time finding what mechanism is thought to be responsible for this side effect in this drug. Can someone please enlighten me?