While the meta-study only reviewed studies about blocking the 5-HT3 receptor, other studies listed below directly implicate the 5-HT1, 5-HT2 and 5-HT7 receptors as well, which strengthens the hypothesis that serotonin (5-HT) as a whole is the driver of OCD. In addition, consider the fact that the drug Meta-Chlorophenylpiperazine (mCPP) is perhaps the most widely-used and well-researched agent for causing/exacerbating OCD. That drug is also the perfect synthetic surrogate of serotonin – i.e. it is an agonist on most 5-HT receptors, it increases serotonin release, and also acts as an SSRI. Hard to get more serotonergic than this.
https://en.wikipedia.org/wiki/Meta-Chlorophenylpiperazine
The old ergot derivative metergoline – a non-selective serotonin antagonist – has been shown to block the pro-OCD effects of mCPP.
https://pubmed.ncbi.nlm.nih.gov/2018816/
To me at least, the evidence above alone means cased closed on the causes and cures of OCD, but since it is only one study I decided to also add the ones below. If that serotonin-as-a-cause-of-OCD hypothesis is correct, then the current treatment of OCD with the serotonergic SSRI drugs is nothing short of criminally negligent and may explain to a great degree why OCD rates continue rising (especially in children and young adults) – i.e. the rising usage of SSRI drugs by those age groups are likely directly contributing to the rising rates of OCD.
https://academic.oup.com/ijnp/article/8/3/391/910011
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310222/
https://psycnet.apa.org/record/2010-07003-006
https://pubmed.ncbi.nlm.nih.gov/17267119/
“…Pooled 5-HT3R-As outperformed placebo regarding Y-BOCS total score (MD = -5.08, 95% CI = -7.04, -3.12, N = 9, n = 560), Y-BOCS obsession subscale score, Y-BOCS compulsive subscale score, treatment response, and remission rate. Individually, all 5-HT3R-As outperformed placebo regarding Y-BOCS total score (granisetron: MD = -5.59, 95% CI = -8.79, -2.39, N = 3, n = 178, ondansetron: MD = -5.72, 95% CI = -8.06, -3.37, N = 6, n = 331, tropisetron: MD = -2.87, 95% CI = -5.19, -0.550, N = 1, n = 96). However, all-cause discontinuation and incidence of individual adverse events between pooled 5-HT3R-As and placebo were not significantly different. In conclusion, our meta-analysis suggested 5-HT3R-As as efficacious for symptom improvement in individuals with OCD. However, the number of individuals included in each study was small; thus, a replication randomized trial of 5-HT3R-As should be conducted using a larger sample size.”
