Psychopharmacology
January 1, 1987
Kathryn A. Cunningham, J. B. Appel
84 citations
The behavioral effects of LSD are mediated primarily through 5-HT2 serotonin receptors rather than 5-HT1 receptors. In rats trained to discriminate LSD from saline, only the 5-HT agonist quipazine mimicked LSD's effects, while several 5-HT2 antagonists blocked the LSD cue. Putative 5-HT1 agonists did not substitute for LSD, and only the 5-HT2 antagonist spiperone failed to block it. These findings indicate that 5-HT2 neuronal systems are more important than 5-HT1 systems in mediating LSD's discriminative stimulus and possibly other effects.
Brain Research
December 1, 2002
Paul S. Frankel, Kathryn A. Cunningham
41 citations
A low dose of the hallucinogen d-lysergic acid diethylamide (d-LSD) triggers a time- and region-dependent increase in c-Fos protein expression in specific rat forebrain areas. Significant increases in c-Fos-positive cells appeared in the anterior cingulate cortex at 1 hour, the shell of the nucleus accumbens at 1 and 2 hours, the lateral bed nucleus of the stria terminalis at 2 hours, and the paraventricular hypothalamic nucleus at 1, 2, and 4 hours after injection. This pattern suggests that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD.
Frontiers in Pharmacology
January 1, 2023
Leah M Salinsky, Christina R Merritt, Joshua C Zamora et al.
14 citations
Opioid misuse and overdose deaths are a major public health problem involving prescription opioids and potent fentanyl derivatives. Repeated overdose events indicate opioid use disorder (OUD). Opioids reduce pain by activating µ-opioid receptors (MOR) in the central nervous system, and dysregulation of reward circuitry underlies OUD. Serotonin (5-HT) contributes to opioid pharmacology and OUD. There is renewed interest in psychedelic compounds acting through the 5-HT2A receptor (5-HT2AR) for treating substance use disorders. Emerging data suggest MOR and 5-HT2AR crosstalk at cellular levels and in OUD circuitry, offering opportunities for novel pharmacological intervention. This review discusses the opportunities and challenges of using 5-HT2AR agonists as therapeutics for OUD.
Psychopharmacology
August 1, 2025
Leah M Salinsky, Christina R Merritt, Erik J. Garcia et al.
8 citations
A single dose of the psychedelic compound (-)-DOI, which activates the 5-HT2A serotonin receptor, reduced cocaine intake and motivation for cocaine in male rats. The drug made cocaine less rewarding and made rats more sensitive to price increases, effectively devaluing the drug. Blocking the 5-HT2A receptor with M100907 eliminated these effects, confirming the receptor's role. The findings suggest that 5-HT2A receptor-acting psychedelics may hold promise for reducing cocaine use, warranting further preclinical research into their effects on intake and relapse.
Psychedelic Med (New Rochelle)
March 13, 2023
Peter S. Hendricks, Charles D. Nichols, Kathryn A. Cunningham et al.
7 citations
A roundtable discussion among experts traces the history, current state, and future directions of psychedelic medicine. Participants review the early research era of the mid-20th century, the subsequent decades of prohibition, and the recent resurgence of clinical trials exploring psychedelics for mental health conditions. The conversation highlights therapeutic applications of substances such as psilocybin and MDMA, emphasizing their potential to treat depression, PTSD, and addiction. Experts also address challenges including regulatory hurdles, the need for trained therapists, and the importance of integrating these treatments into mainstream healthcare. The discussion concludes with cautious optimism about the field's trajectory.
J Med Chem
May 1, 2025
Saghir Ali, Xiaochen Tian, Kathryn A. Cunningham et al.
5 citations
The 5-HT2A receptor is a key target for psychedelic drugs, and research is exploring its role in developing new treatments for psychiatric disorders. This review examines the receptor's structure, function, and signaling pathways, highlighting how psychedelics like psilocybin and LSD interact with it to produce their effects. The authors discuss potential therapeutic applications beyond psychedelic experiences, including for depression, anxiety, and addiction, while also considering the challenges of designing drugs that retain therapeutic benefits without hallucinogenic side effects. The work synthesizes current knowledge on 5-HT2A receptor pharmacology and its implications for drug development.
Journal of Medicinal Chemistry
September 25, 2025
Saghir Ali, Xiaochen Tian, Kathryn A. Cunningham et al.
2 citations
Psychedelics demonstrate significant potential in influencing behavior by targeting neurotransmitter receptors. In a study involving 150 participants, 70% reported enhanced emotional well-being after using specific alkaloids derived from benzene derivatives. The pharmacological effects were linked to improved cognitive flexibility and reduced anxiety. Chemical synthesis methods revealed that certain compounds exhibited up to a 50% increase in biological activity compared to traditional treatments. These findings underscore the promise of psychedelics in therapeutic settings, paving the way for innovative drug studies in mental health.
American Psychiatric Publishing eBooks
May 5, 2014
Robert N. Pechnick, Kathryn A. Cunningham, Itai Danovitch
Hallucinogens are a class of psychoactive drugs, either synthetic or plant-derived, that produce auditory or visual hallucinations and alter thought, mood, and perception. Depending on dosage, user expectation (set), and environment (setting), they can also induce euphoria or a state similar to a transcendental experience. Some hallucinogens, like jimsonweed, cause delirium with disturbances in judgment and memory, while others, such as LSD, psilocybin, DMT, and mescaline, alter consciousness without delirium or sedation. These serotonergic hallucinogens primarily affect the serotonin receptor system. Other plant products with hallucinogenic activity include morning glory seeds and Hawaiian baby woodrose seeds, which contain lysergic acid derivatives.