See this article in JAMA Psych - http://app.jamanetwork.com/?doi=10.1001/jamapsychiatry.2015.0546&utm_source=email&utm_medium=app&utm_campaign=share -- raises the obvious question of whether cycloserine can be a useful medication, with or without CBT. I am wondering if any addiction docs have Rx-ed cycloserine as part of psychopharmacology for SUD pts. Thank you.
The article you posted talks about using d-cycloserine for OCD. Sounds like using it for addictions would be an experimental proposal.
When prescribed for phobias, D-cycloserine binds to the glycine site of the NMDA receptor, which allows glutamate (released during exposure therapy) to bind to the glutamate site of the NMDA receptor, thereby facilitating glutamate neurotransmission in circuits involved in fear extinction in the amygdala. The glycine site needs to be occupied by either glycine or D-cycloserine, in order for glutamate transmission to occur at NMDA receptors. So utilizing D-cycloserine without exposure therapy would not be helpful for fear extinction, given glutamate is needed for this NMDA receptor-mediated, fear extinction circuit. Glutamate is released with exposure therapy, so this combination of D-cycloserine and exposure is the key for fear extinction in specific phobia (and in the study you reference, D-cycloserine with CBT for OCD). When using D-cycloserine without exposure or CBT, glutamate is not released, and fear extinction does not occur, as the D-cycloserine is just occupying the glycine site of the NMDA receptor, and no glutamate is present to complete the transmission in the fear extinction circuit.
As for the other question you raised, substance use disorders involve the reward circuits mediated by the mesolimbic dopamine pathway. So addictions would be a dopamine-mediated process.
Dr. Carandang,
Thank you for clarifying the neurophysiology of D-cycloserine. I suppose by itself (without CBT/exposure) cycloserine would not hold much promise. This raises the question of whether it would have any efficacy in fear extinction if it were administered in CONJUNCTION with a medication that augments glutamate.
I agree that there is a general consensus that SUDs are governed by the mesolimbic dopamine pathway, and there is promising research on this mechanism of action with several substances of misuse (primarily nicotine) as it is very difficult to get studies on some substances of misuse by an IRB for obvious reasons. I wonder if ALL addictive disorders are dopamine-mediated?
Do you know if anyone in the clinical community is prescribing GLUTAMATERGIC drugs to aid in the treatment of SUDs? My view is that Addictive Disorders, as so defined in the DSM5, have many commonalities with OCD in terms of pt behavior - e.g. obsessions, compulsions to use a substance. I know, for example, that some clinicians use high dose (300mg+/day) pregabalin (LYRICA) to reduce cravings in pts experiencing PAWS (Post Acute Withdrawal Syndrome) after cessation of long-term opioid use.
For present purposes, I am more concerned with actual clinical Tx/Rx in the addiction medicine community, as opposed to etiology/neurophysiology of addiction, as I think it will be quite a long time before the latter leads to effective psychopharmacological options when dealing with substances, such as opioids, in which there is limited insight as to the mediating pathways.
So far pregabalin has been explored with limited success in OCD. See for example: Oulis P, Mourikis I, Konstantakopoulos G. Pregabalin augmentation in treatment-resistant obsessive–compulsive disorder. Int. Clin. Psychopharmacol. 26(4),221–224 (2011) and Di Nicola M, Tedeschi D, Martinotti G et al. Pregabalin augmentation in treatment-resistant obsessive–compulsive disorder: a 16-week case series. J. Clin. Psychopharmacol. 31(5),675–677 (2011).
Thank you for your very helpful response.
There have been a few studies looking at this in terms of cue reactivity/craving-
See:
http://link.springer.com/article/10.1007/s00213-011-2592-x
http://informahealthcare.com/doi/abs/10.3109/00952990903384332
http://www.ncbi.nlm.nih.gov/pubmed/19592176
http://www.ncbi.nlm.nih.gov/pubmed/21318564
However, keep this in mind https://www.researchgate.net/publication/228100311_Maintaining_Clinical_Relevance_Considerations_for_the_Future_of_Research_into_D-Cycloserine_and_Cue_Exposure_Therapy_for_Addiction
http://www.ncbi.nlm.nih.gov/pubmed/21455709
Article Maintaining Clinical Relevance: Considerations for the Futur...
N acetyl cysteine has glutamatergic mechanisms (among many other actions) and has been found useful in cannabis dependence as well as other SUDs (in addition to many other potential neuropsychiatric indications). Cheap, safe, OTC nutritional supplement with good RCT evidence base, and seems to help some of my patients.