Disclaimer: I am not a doctor, and this is not medical advice. Do not take any medication without appropriate medical supervision.

Anti-high

One of the most fascinating articles I’ve ever read is “New Frontiers of Sobriety” by Hamilton Morris of VICE. 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.

Morris then takes large doses of these compounds in isolation, finding each to be a broadly uncomfortable experience. 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.

Lamotrigine: the anti-ketamine

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. 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”). Like most dissociatives, such as PCP and DXM, ketamine acts as an antagonist at the NMDA receptor, and stimulates release of the neurotransmitter glutamate. Conversely, lamotrigine functions as an inhibitor of glutamate release, and has been found to lessen the effects of ketamine, including depersonalization and derealization.

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. Depersonalization disorder is highly distressing to sufferers and associated with a wide array of negative mental health and social outcomes. It’s also something I struggled with for most of my life.

My life with depersonalization

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. As a child I just didn’t really see the point of practically anything I was doing, or that anyone else was doing; it held no real emotional resonance or meaning for me. Whatever interests I chose to pursue felt more like an obligatory way of filling time, not something that had any value or importance in its own right. I always felt the lack of spontaneity characteristic of depersonalization disorder, and whenever I chose to say anything, it felt rehearsed and acted out as if I had to engage my every word and action manually. Most of the time I would choose to say nothing at all. My feelings seemed to be kept at a distance, happening as something separate from an interior “me” who didn’t truly experience these emotions and seemingly couldn’t be touched by them. I was painfully conscious of all of these things.

Most sufferers of chronic depersonalization experience its onset at adolescence, while others have faced these symptoms for as long as they can remember. I was unlucky enough to experience both. The onset of puberty brought with it a deeper and even more malignant spectrum of depersonalization symptoms, and I can pinpoint when it happened. I was 13, and it was fall of 2002, about halfway through the first semester of sophomore year. One day, as if overnight, I simply stopped feeling anything. If there were any emotions present in me, they were now so far removed that I could no longer see them at all. When I would try to cry, it felt like trying to force a physical function more than any natural expression of emotion; when I would try to feel angry, it seemed so hollow and utterly perfunctory. The world itself seemed to have faded away in some sense, like a video game level that I was moving around in while not actually being part of it. The profound numbness lasted for more than a year, and in this state, I couldn’t gather any motivation to do what was expected of me. I ignored my homework and filled in random answers on tests; getting in trouble with my parents and faculty simply meant nothing to me. I dropped out right before junior year.

When everything changed

The utter emotional deadness faded somewhat over my teenage years, and I found various ways to distract myself from the feeling that everything was just very wrong. Music could bring me a brief uplift, and it was one of the only things that helped to keep me alive through this time. I started training myself to disrupt my ruminating thoughts by immediately shifting my attention to something else. I started a YouTube channel and forced myself to create new videos every day or two, as a way of running and keeping ahead of the emptiness always threatening to envelop me. I was afraid that if I ever stopped, it would consume my entire life again. Developing a feminine presentation in my videos was one of the first things I ever decided to do for its own sake, simply because I wanted to – something that had evaded me for all of my life. Still, any real emotion felt out of my reach, and I continued to feel separated from the world as if by some elastic skin that I could never pierce. I wanted so badly just to touch the real world and finally feel alive, whatever that would feel like.

After a lengthy period of consideration and living as a woman, in 2012 I concluded that I needed to start HRT. I realized I wouldn’t be comfortable at all with my body continuing to masculinize throughout my life, and I was also curious about how HRT might affect my mood. There was very little information available on its emotional effects aside from isolated references to feeling like one’s brain is “running on the right fuel”, so I had no reason to expect that within a week or two after starting hormones, those lifelong symptoms of depersonalization and derealization would dissolve completely. I had no idea HRT could do that – I didn’t even think it was possible for me to feel anything other than that constant dislocation from myself and the world. This was a revelation more significant to me than anything else in my life before or since. The skin could be pierced, there was a real world out there full of depth and richness and life, and I could be part of it – as real a person as everyone else, at last. I wasn’t hollow after all, and neither was the world; everything became so fleshed out with meaning. For the first time, there was a point to life: not just filling time running out the clock, but discovering there were things that really mattered to me, things worth working towards and the true satisfaction that came with it. I’ve accomplished more since transitioning than I did in my entire life before, and I’ve never been happier. My life matters now.

The right fuel

Since experiencing this completely unexpected shift in my consciousness, I’ve been deeply interested in what the physical basis for this change could be. While research on HRT in trans people consistently indicates that it can relieve depressive and anxious symptoms, very little information is available on the biological basis of depersonalization symptoms, let alone the specifics of how depersonalization disorder can affect trans people. Medical transition, particularly HRT, is associated with a reduction in depersonalization and derealization – but how? Intriguingly, estrogen itself modulates NMDA receptors, and some of its effects can be blocked by NMDA antagonists (implicated in the effects of dissociative drugs). Estrogen has also shown some success in treating the negative symptoms of schizophrenia, which have a degree of phenomenological overlap with experiences of depersonalization. There are many pieces that seem relevant here, but as of yet very little to fit them together into a more complete model of how the action of estrogen can treat depersonalization (and even less to explain how testosterone treatment is equally successful at reducing depersonalization in trans men).

In short, these phenomena fascinate me, and there is an urgent need for more research into these areas given the severe impact of this syndrome on those trying to bear this living death. Depersonalization wrecked my life, draining it of all the promise it supposedly held. It stole my soul without the courtesy of killing me. If there is anything that can help us fight back against this condition, that matters.

And that’s why I decided to try lamotrigine.

Next: Part 2: The experience.