Pregnenolone sulfate is an endogenous neurosteroid with excitatory effects in the brain, acting as a potent negative allosteric modulator of the GABAA receptor, a positive allosteric modulator of the NMDA receptor, and activator of transient receptor potential cation channel TRPM1 and TRPM3. In the model of schizophrenia, treatment with pregnenolone sulfate normalized the hyperlocomotion and stereotypic bouts, and rescued the PPI deficits of dopamine transporter knockout mice. Promnesic properties of pregnenolone sulfate were demonstrated in rat models of spatial memory performance.

Pregnenolone sulfate is an endogenous neurosteroid with excitatory effects in the brain, acting as a potent negative allosteric modulator of the GABAA receptor, a positive allosteric modulator of the NMDA receptor, and activator of transient receptor potential cation channel TRPM1 and TRPM3. In the model of schizophrenia, treatment with pregnenolone sulfate normalized the hyperlocomotion and stereotypic bouts, and rescued the PPI deficits of dopamine transporter knockout mice. Promnesic properties of pregnenolone sulfate were demonstrated in rat models of spatial memory performance.

Nabiximols (USAN, trade name Sativex) is a specific extract of Cannabis that was approved as a botanical drug in the United Kingdom in 2010 as a mouth spray to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms of multiple sclerosis. Nabiximols is an oromucosal spray of a formulated extract of the cannabis sativa plant that contains the principal cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD) as well as specific minor cannabinoids and other non-cannabinoid components. THC is a partial agonist and can block activation by other ligands of both cannabinoid receptors (CBR). THC effects include analgesia, short-term memory loss, muscle relaxation, antiemesis, appetite stimulation, and anti-inflammatory activity. CBD acts on CBR and TRPV1, while also inhibiting reuptake and hydrolysis of anandamide N-arachidonylethanolamine (AEA). CBD effects include anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, antioxidant, anti-inflammatory, immunomodulatory and anti-psychotic activity. CBD modulates some of the more undesirable psychological adverse effects of THC through both pharmacokinetic and pharmacodynamic effects. Each 100 μl spray contains: 2.7 mg of THC and 2.5 mg of CBD. Nabiximols was approved in other European countries and Canada.

Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) was an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects. Rimonabant is an inverse agonist for the cannabinoid receptor CB1 and was the first drug approved in that class. There is considerable evidence that the endocannabinoid (endogenous cannabinoid) system plays a significant role in appetitive drive and associated behaviors. It is, therefore, reasonable to hypothesize that the attenuation of the activity of this system would have therapeutic benefit in treating disorders that might have a component of excess appetitive drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders. Data from clinical trials submitted to regulatory authorities showed that rimonabant caused depressive disorders or mood alterations in up to 10% of subjects and suicidal ideation in around 1%, and in Europe, it was contraindicated for people with any psychiatric disorder, including depressed or suicidal people. Additionally, nausea and upper respiratory tract infections were very common (occurring in more than 10% of people) adverse effects; common adverse effects (occurring in between 1% and 10% of people) included gastroenteritis, anxiety, irritability, insomnia and other sleep disorders, hot flushes, diarrhea, vomiting, dry or itchy skin, tendonitis, muscle cramps and spasms, fatigue, flu-like symptoms, and increased risk of falling.