One of the classic symptoms of depression is anhedonia, or the loss of interest and pleasure in activities that were previously interesting or rewarding. Anhedonia also self-perpetuates depression, as the loss of desire to participate in rewarding activities leads to further sadness, isolation, and lack of motivation. People with other mental illnesses also frequently suffer from anhedonia, yet it remains very difficult to treat.
Conversational therapy, pharmaceutics and electric stimulation procedures are currently approved as conventional therapy. Psychotherapeutic approaches to anhedonia are costly, time-consuming and have variable outcomes. Antidepressant medications have mixed results and typically take a few weeks to produce a measurable effect. Electroconvulsive therapy and similar procedures are invasive, carry risk and also take repeated treatments to determine effectiveness. However, ketamine has been shown to be a fast and effective treatment for severe and treatment-resistant depression.
Ketamine has long been used safely in clinical settings as an anesthetic. Ketamine is potent, fast-acting, and proven safe in clinical settings. Recently, it has been shown to also provide long-acting relief from depressive symptoms for patients with anhedonia. Because of the potential for hallucinations, muscle paralysis and cardiopulmonary depression, ketamine is not currently being prescribed as a treatment for anhedonia. It can also cause bladder problems and be habit forming when used often enough.
The street version of ketamine, called “K” or “Vitamin K” has gained popularity since the 1990s, presumably for its antidepressant and spiritual effects. Hallucinations and “out-of-body” experiences are common. Overdoses and deaths have also been reported. More work was needed to better understand the effect of ketamine on the brain.
Scientists recently used ketamine to gain insight into the underlying mechanisms that produce feelings of pleasure in the brain. In this study, rodents were genetically modified so their brains could be manipulated by light (optogenetics). Brain function and behavior were observed during ketamine administration. The researchers were able to manipulate brain circuits also using optogenetics, to determine which parts of the brain produced the beneficial effects of ketamine and which produced the negative effects. Ketamine was found to cause activation and changes in the circuitry that resulted in plasticity, which is perhaps why the resulting antidepressive effects are long lasting. These results have implications for the development of targeted treatments without unpleasant or dangerous side effects.
Other psychedelic drugs
Ketamine is not the only hallucinogenic medication that has been considered beneficial in the treatment of mental health disorders. Other psychadelics, deliriants and dissociative agents have also been reported to improve anhedonia with lasting effects and no habit formation. In fact, some people with substance abuse disorders report that they were able to decrease or discontinue substance use after experiencing positive spiritual effects from these drugs. Some psychadelics that occur naturally include:
Psilocybin found in some mushrooms
Ayahuasca from a South American vine
Mescaline from peyote cactus
These natural psychadelics have been used throughout the ages in traditional spiritual ceremonies throughout the globe. In the United States, all are illegal but peyote for religious exceptions. More dangerous are manufactured psychadelics, such as the illicit drugs lysergic acid (LSD) and phencyclidine (PCP). Legal synthetics include the powerful dissociative dextromethorphan (DXM) found in cough medicine, and the deliriants diphenhydramine and dimenhydrinate. Further study into the mechanism of action of these drugs may bring us even closer to a cure for anhedonia.
On the cutting edge
Leading centers are currently conducting studies in humans on psychedelics in the treatment of depression, alcoholism and other mental disorders. These include New York University, Johns Hopkins University, UCLA, the University of New Mexico, Imperial College of London and the University of Zurich. Perhaps soon, a safe and effective treatment of anhedonia will become legal and available to the millions who still suffer.
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Written by Dana Connolly, Ph.D., Sovereign Health Group staff medical writer
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