There was no point where I didn’t feel somehow removed from the world around me - this disconcerting sensation was present from my earliest memories. It’s also something I struggled with for most of my life. Depersonalization disorder is highly distressing to sufferers and associated with a wide array of negative mental health and social outcomes. Lamotrigine in combination with SSRIs is also one of the very few approaches that has shown some efficacy in treating chronic depersonalization, the syndrome of unremitting depersonalization and derealization symptoms that can last for decades. Conversely, lamotrigine functions as an inhibitor of glutamate release, and has been found to lessen the effects of ketamine, including depersonalization and derealization. Like most dissociatives, such as PCP and DXM, ketamine acts as an antagonist at the NMDA receptor, and stimulates release of the neurotransmitter glutamate. The dissociative anesthetic ketamine, often used as a recreational drug, induces pronounced symptoms of depersonalization and derealization (emotional blunting, feelings that one has “no self”, and a sense that the world is “unreal”).

One anti-high that Morris did not explore is the closest thing to an “anti-ketamine”: lamotrigine (Lamictal), an anticonvulsant and mood stabilizer used to treat epilepsy and bipolar disorder, along with experimental uses for schizophrenia, depression, and borderline personality disorder. Rimonabant is a potent appetite suppressant with unpleasant physical and psychiatric side effects, risperidone is heavily sedating, and naltrexone produces sensations he describes as “Wow, am I on edge!” None of them sound even remotely enjoyable to use whether medically indicated or not. Morris then takes large doses of these compounds in isolation, finding each to be a broadly uncomfortable experience. Morris describes several medications which have an effect roughly opposite to various recreational drugs: rimonabant, a cannabinoid receptor blocker that also works against the action of the body’s endogenous cannabinoids risperidone, an atypical antipsychotic that counteracts many of the effects of LSD and naltrexone, an opioid antagonist used to manage opioid dependence by blocking the action of drugs like heroin and fentanyl - as well as natural endorphins. One of the most fascinating articles I’ve ever read is “New Frontiers of Sobriety” by Hamilton Morris of VICE. Previously: Depersonalization in gender dysphoria: widespread and widely unrecognized Anti-high Do not take any medication without appropriate medical supervision.

Trip report: Lamotrigine, a drug to treat depersonalizationĭisclaimer: I am not a doctor, and this is not medical advice.

Depersonalization disorder treatments