Background: The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs, and offers a unified account of the acute and therapeutic action of psychedelics. Although REBUS has received some neuroscientific support, little research has examined its psychologic...
The effects of psychedelic drugs in headache and chronic pain disorders have been reported for several decades, and now controlled studies are emerging. The existing evidence supports a lasting therapeutic benefit after limited dosing, a unique feature of the drug class that distinguishes it from conventional treatment. This commentary summarizes these repor...
Ketamine, a non-competitive NMDA inhibitor with significant psychedelic properties, is widely used in the management of acute and chronic pain. Ketamine is used intraoperatively to spare opioids and prevent acute and chronic postoperative pain; it is also used in patients with complex pain syndromes and patients with opioid tolerance. Medical cannabis is alr...
Recent trials with psychedelics in major depressive disorder and treatment-resistant depression showed remarkable improvements in depressive symptoms that can last for up to several months after even a single administration. The lack of an appropriate placebo control group-as patients are often able to discriminate the subjective effects of the drug-and an i...
Post-traumatic stress disorder (PTSD) is a debilitating mental illness with limited treatment options and a high treatment dropout rate. Psychedelics, often in combination with psychotherapy, are now under investigation as a potential treatment option for a variety of psychiatric conditions including PTSD. This paper reviews the proposed mechanism of action ...
Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Function...
Psilocybin-containing mushrooms have been consumed by various cultures in many different parts of the world for thousands of years. Psilocybin, a classic psychedelic, contains unique psychoactive properties and has been incorporated into religious ceremonies and investigated for its medicinal value. In the mid-20th century, psilocybin, along with most other ...
“Are magic mushrooms the miracle cure for depression we've been looking for?” (Khan, 2021). Attention-grabbing headlines such as this are becoming increasingly common and suggest that psychedelic medicines are some kind of magic bullet. This perception is increased by stories of people who had a single life-changing psychedelic experience that resulted in co...
Obsessive-compulsive disorder (OCD) is a highly prevalent and disabling condition for which currently available treatments are insufficiently effective and alternatives merit priority attention. Psilocybin may represent a safe and effective avenue for treatment of individuals affected by this condition. In this chapter we briefly introduce OCD symptoms, epid...
Substance use disorders (SUD) represent a significant public health issue with a high need for novel and efficacious treatment options. In light of this high unmet need, recent results reporting beneficial outcomes of psychedelic-assisted therapy in SUD are particularly relevant. However, several questions remain with regard to this treatment approach. The c...
The therapeutic potential of psychedelics in headache and chronic pain disorders is documented over decades of anecdotal and early investigational reports, which have paved the way for the first controlled studies of psilocybin and lysergic acid diethylamide (LSD) in these disorders. The reported lasting clinical effects after limited dosing with psychedelic...
Current treatment options for major depressive disorder (MDD) have limited efficacy and are associated with adverse effects. Recent studies investigating the antidepressant effect of serotonergic psychedelics-also known as classic psychedelics-have promising preliminary results with large effect sizes. In this context, we conducted a review of the putative n...
Synaptopathies (Fall, 2022) Synaptic neurotransmission lies at the heart of nervous system's functioning. Clearly then, alterations in synaptic signal transduction can lead to a variety of neural disorders. Perhaps the most widely known of these disorders include certain movement disorders and myasthenia gravis. More recent interest in synaptic dysfunction h...
There has recently been a renewal of interest in psychedelic research on the use of psilocybin in psychiatric treatment and, in particular, for the treatment of major depressive disorder (MDD). Several state-of-the-art studies have provided new insight into the mechanisms of action of psilocybin and its therapeutic potential. Nevertheless, many questions rem...
The emerging therapeutic efficacy of ketamine and classical psychedelics for depression has inspired tremendous interest in the underlying neurobiological mechanisms. We review preclinical and clinical evidence supporting neuroplasticity as a convergent downstream mechanism of action for these novel fast-acting antidepressants. Through their primary glutamat...
The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor-receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical anti...
Aims Depression is the single largest contributor to global disability. However, effective treatments are currently lacking, resulting in a significant burden of treatment-resistant depression (TRD). Psilocybin, a serotonergic psychedelic, found as the active compound in 'magic mushrooms', has been proposed as a novel therapeutic avenue for TRD. We aimed to ...
Aims Depression is the single largest contributor to global disability. However, effective treatments are currently lacking, resulting in a significant burden of treatment-resistant depression (TRD). Psilocybin, a serotonergic psychedelic, found as the active compound in 'magic mushrooms', has been proposed as a novel therapeutic avenue for TRD. We aimed to ...
Objective: Recent clinical trials have demonstrated that psilocybin may have strong antidepressant effects, and may be effective in the treatment of depressive disorders when embedded in a psychotherapeutic protocol (psilocybin-assisted psychotherapy; PAP). However, despite promising results, the mechanism(s) that may be responsible for the antidepressant ef...