New LSD study opens depression treatment path using opioid system for major depression relief. Researchers at Imperial College London recently published images of the brain under the influence of lysergic acid diethylamide (LSD) from their research set to explore the effects of psychedelic drugs.
For the study, the researches selected participants with a prior history of LSD use. The subjects received either 75 micrograms of LSD or a drug-free placebo. After the injection, the participants underwent a series of tests. The researchers used functional MRI scans to look at areas with increased blood flow. They found a slight increase of the blood flow to the visual cortex, which led to hallucinations experienced while on LSD.
The researchers also used an alternative imaging technique known as magnetoencephalography in order to track the electrical activity in the brain. The researchers noted the changes in the brain’s synchrony, which is the neurons’ ability to fire together. They found that the areas of the brain that usually fire all their neurons in sync stopped doing so under the influence of LSD, while other areas that usually do not fire their neurons together started doing so.
After the brain scans, the researchers gave the participants questionnaires to document their experiences while on LSD. The researchers found ego-dissolution, a feeling of connection with the world around them rather than as a separate entity, is associated with a reduction of brain synchrony.
The researchers also uncovered that brain areas that are normally disconnected began communicating with one another while on LSD. Under the influence of psychedelics, the parahippocampus started sending messages to the visual cortex, resulting in vivid imagery and memories. This led researchers to conclude that psychedelics have the ability to disrupt the brain’s default-signaling pathways, which are very strong in people with depression.
Based on these findings, the researchers suggest that psychedelics may be useful in the treatment of depression in cases where the patient is resistant to antidepressants and other traditional treatment methods. These results not only help us better understand the brain, but open a door to possible new treatments for mental illness.
Opioid system may help relieve treatment-resistant major depression
A recent clinical trial of an experimental drug treatment for depression patients that are resistant to antidepressants revealed that the use of opioids may help improve the effectiveness of drugs that target the action of serotonin and related monoamine neurotransmitters. The researchers found that the new drug, known as ALKS-5461, could have complementary effects on different opioid receptors – when added to serotonin-targeting antidepressant therapy. The combination of drugs produced significant symptom improvement in patients with persistent depression.
Executive director Dr. Maurizio Fava said, “We know that more than half of patients with major depression won’t respond to the first antidepressant they try, and almost 40 percent will continue to have symptoms even after switching to or adding different drugs. Opioids have actually been used for centuries to treat mood disorders, and while opioid drugs must be used cautiously because of their potential for abuse, studies have shown that levels of the endogenous opioids released by the central nervous system may be reduced in important brain areas of patients with major depression.”
The study, which is a phase two clinical trial, enrolled 142 patients with treatment-resistant depression. The trial was conducted in two stages: in stage one, 98 participants were randomized to receive placebo doses while 43 participants received ALKS-5461 in daily dosages containing either 2 mg or 8 mg of each of the two drugs.
After the first stage, the placebo participants who did not show any improvement were re-randomized to receive one of the two dosages of the active drug or to continue receiving a placebo for stage two.
Fava explained, “The robust treatment effect seen in this clinical study suggests that many patients with depression may have a dysregulation of the endogenous opioid system, which may be why they do not respond to monoamine-based antidepressants that target the serotonin system. For the substantial percentage of patients who do not respond to monoamine-based medications, this combination may represent an important new approach to the treatment of depression.”
Phase three testing in the clinical trial has also been completed, but the results have not been posted yet.
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