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Psychology

Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study

January 13, 2015 / Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.

Bogenschutz, M. P., Forcehimes, A. A, Pommy, J. A., Wilcox, C. E., Barbosa, P. C. R., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114565144

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Making a medicine out of MDMA

January 5, 2015 / Anxiety Disorders / PTSD, MDMA, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

From its first use 3,4,-methylenedioxymethamphetamine (MDMA) has been recognised as a drug with therapeutic potential. Research on its clinical utility stopped when it entered the recreational drug scene but has slowly resurrected in the past decade. Currently there is enough evidence for MDMA to be removed from its Schedule 1 status of ‘no medical use’ and moved into Schedule 2 (alongside other misused but useful medicines such as heroin and amphetamine). Such a regulatory move would liberate its use as a medicine for patients experiencing severe mental illnesses such as treatment-resistant post-traumatic stress disorder.

Sessa, B., & Nutt, D. (2015). Making a medicine out of MDMA. The British Journal of Psychiatry, 206, 4-6. https://dx.doi.org/10.1192/bjp.bp.114.152751

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Can psychedelic compounds play a part in drug dependence therapy?

January 5, 2015 / Ayahuasca, Iboga / Ibogaine, Ketamine, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area.

Sessa, B., & Johnson, M. W. (2015). Can psychedelic compounds play a part in drug dependence therapy? The British Journal of Psychiatry, 206, 1-3. https://dx.doi.org/10.1192/bjp.bp.114.148031

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Psychedelic-facilitated smoking cessation: An online survey

January 1, 2015 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Aims:
Pilot laboratory results suggest psilocybin may be an efficacious adjunct to smoking cessation treatment. However, no study has examined smoking cessation after psychedelic use in naturalistic settings.
Methods:
We are conducting an online survey collecting demographics, smoking history, and other data from people who self-report quitting/reducing smoking after taking a psychedelic.
Results:
Among current completers (N=164), LSD (49%) and psilocybin (32%) were the drugs most commonly associated with quitting/reducing, with a mode of 2-5 lifetime uses each. Participants reported smoking a mean of 12 cigs/day for a mean of 8 yrs before the experience. 62(38%) reported total and continuing abstinence after their experience, with 29 of the 62 (47%) reporting >1yr abstinence, and 7 (11%) reporting >10 yrs abstinence. Another 67 of the 164 (41%) reported persisting smoking reduction, from a mode of 10-20 cigs/day before, to a mode of <1 cig/month after the experience. The remaining 35 (21%) reported temporary reduction, with 6 of the 35 (17%) reporting >1 yr reduction. Although the majority of withdrawal symptoms were rated as equal in severity to previous quit attempts, depression, irritability, anxiety, and craving were rated as “much less severe.” 141 of the 164 (86%) reported no premeditated intention to quit/reduce smoking, and 159 (97%) described their experience as highly meaningful, with
97 (59%) considering it among the 10 most meaningful experiences of their lives. Participants cited changed life priorities/values (26%), strengthened belief in their ability to quit (26%), and changed future orientation (17%) as the most important effects leading to quitting/reducing. Other changes reported after psychedelic use included reduced alcohol (38%) and other drug use (23%).
Conclusions:
Psychedelics may prompt temporary or prolonged smoking cessation, suggesting that careful administration in a treatment context may enhance motivation in changing addictive behaviors. Psychological and neurobiological mechanisms underlying such behavioral changes require further investigation.

Garcia-Romeu, A. P., Griffiths, R. R., & Johnson, M. W. (2015). Psychedelic-facilitated smoking cessation: An online survey. Drug and Alcohol Dependence, (146), e120. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.245
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Ketamine interactions with biomarkers of stress: A randomized placebo-controlled repeated measures resting-state fMRI and PCASL pilot study in healthy men

December 29, 2014 / Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Ketamine, an NMDA receptor antagonist, is increasingly used to study the link between glutamatergic signaling dysregulation and mood and chronic pain disorders. Glutamatergic neurotransmission and stress corticosteroids (cortisol in human) are critical for Ca2 + mediated neuroplasticity and behavioral adaptation. The mechanisms of action of glutamatergic neurotransmission and stress corticosteroids on the NMDA-receptors of the hippocampus have been long studied in animals, but given little attention in human studies. In this randomized single-blinded placebo-controlled crossover study (12 healthy young men), five sets of resting-state fMRI (RSFMRI), pseudocontinuous arterial spin labeling (PCASL), and corresponding salivary cortisol samples were acquired over 4 h, at given intervals under pharmacokinetically-controlled infusion of subanesthetic ketamine (20 & 40 mg/70 kg/h). An identical procedure was repeated under a sham placebo condition. Differences in the profile of ketamine versus placebo effect over time were examined. Compared to placebo, ketamine mimicked a stress-like response (increased cortisol, reduced calmness and alertness, and impaired working memory). Ketamine effects on the brain included a transient prefrontal hyperperfusion and a dose-related reduction of relative hippocampal perfusion, plus emerging hyperconnectivity between the hippocampus and the occipital, cingulate, precuneal, cerebellar and basal ganglia regions. The spatiotemporal profiles of ketamine effects on different hippocampal subnetworks suggest a topographically dissociable change in corticohippocampal functional connectivity. We discuss our findings in the context of the negative feedback inhibition theory of the hippocampal stress control. This pilot study provides a methodological framework for multimodal functional neuroimaging under resting-state conditions, which may be generalized for translational studies of glutamatergic- or stress-related etiology of neuropsychiatric disorders.

Mahani, N. K., Niesters, M., van Osch, M. J., Oitzl, M., Veer, I., de Rooij, M., … & Dahan, A. (2014). Ketamine Interactions with Biomarkers of Stress: A randomized placebo-controlled repeated measures resting-state fMRI and PCASL pilot study in healthy men. NeuroImage. https://dx.doi.org/10.1016/j.neuroimage.2014.12.050
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Rapid-onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression

December 26, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Summary

What is known and objective

The current pharmacotherapeutic treatment of major depressive disorder (MDD) generally takes weeks to be effective. As the molecular action of these drugs is immediate, the mechanistic basis for this lag is unclear. A drug that has a more rapid onset of action would be a major therapeutic advance and also be a useful comparator to provide valuable mechanistic insight into the disorder and its treatment.

Comment

Recent evidence suggests that ketamine produces rapid-onset antidepressant action. Important questions are as follows: is it specific or coincidental to other effects; is there a dose–response relationship; and is the mechanism related to that of current antidepressants. NMDA receptor antagonism is unlikely the explanation for ketamine’s antidepressant action.

What is new and conclusion

It is not an exaggeration to state that the new findings, if validated, might produce a revolution in understanding and treating depressive disorders.

Drewniany, E., Han, J., Hancock, C., Jones, R. L., Lim, J., Nemat Gorgani, N., … & Raffa, R. B. (2014). Rapid‐onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression. Journal of Clinical Pharmacy and Therapeutics. https://dx.doi.org/10.1111/jcpt.12238
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Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial

December 17, 2014 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the potential for adverse neurocognitive effects in this population has not received adequate study. The current study was designed to investigate the delayed neurocognitive impact of ketamine in TRD and examine baseline antidepressant response predictors in the context of a randomized controlled trial. In the current study, 62 patients (mean age=46.2±12.2) with TRD free of concomitant antidepressant medication underwent neurocognitive assessments using components of the MATRICS Consensus Cognitive Battery (MCCB) before and after a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg). Participants were randomized to ketamine or midazolam in a 2:1 fashion under double-blind conditions and underwent depression symptom assessments at 24, 48, 72 h, and 7 days post treatment using the Montgomery–Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive assessment was conducted once at 7 days. Neurocognitive performance improved following the treatment regardless of treatment condition. There was no differential effect of treatment on neurocognitive performance and no association with antidepressant response. Slower processing speed at baseline uniquely predicted greater improvement in depression at 24 h following ketamine (t=2.3, p=0.027), while controlling for age, depression severity, and performance on other neurocognitive domains. In the current study, we found that ketamine was devoid of adverse neurocognitive effects at 7 days post treatment and that slower baseline processing speed was associated with greater antidepressant response. Future studies are required to further define the neurocognitive profile of ketamine in clinical samples and to identify clinically useful response moderators.

Murrough, J. W., Burdick, K. E., Levitch, C. F., Perez, A. M., Brallier, J. W., Chang, L. C., … & Iosifescu, D. V. (2014). Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial. Neuropsychopharmacology. https://dx.doi.org/10.1038/npp.2014.298

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Nitrous Oxide for Treatment-Resistant Major Depression: a Proof-of-Concept Trial

December 9, 2014 / Depressive Disorders, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background

NMDA receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and NMDA receptor antagonist, may also be a rapidly acting treatment for TRD.

Methods

In this blinded, placebo-controlled crossover trial 20 TRD patients were randomized to a 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). Primary endpoint was the change on HDRS-21 24 hours after treatment.

Results

Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) minutes at a median inspiratory concentration of 44% (37 – 45%, IQR). In two patients nitrous oxide treatment was briefly interrupted and in three discontinued. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared to placebo (mean HDRS-21difference at 2 hours: -4.8 points, 95% CI -1.8 to – 7.8 points, p= 0.002; at 24 hours: -5.5 points, 95% CI -2.5 to -8.5 points, p<0.001; comparison between nitrous oxide and placebo: p<0.001). Four patients (20%) had treatment response (reduction ≥50% on HDRS); three patients (15%) a full remission (HDRS ≤ 7 points) after nitrous oxide, compared to one patient (5%) and none after placebo (odds ratio [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][OR] for response 4.0, 95% CI 0.45 – 35.79; OR for remission 3.0, 95% CI 0.31 – 28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity.

Conclusions

This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with treatment-resistant depression.

Nagele, P., Duma, A., Kopec, M., Gebara, M. A., Parsoei, A., Walker, M., … & Conway, C. (2014). Nitrous Oxide for Treatment-Resistant Major Depression: a Proof-of-Concept Trial. Biological Psychiatry. https://dx.doi.org/10.1016/j.biopsych.2014.11.016
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Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

November 29, 2014 / LSD, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , , ,

Abstract

Background

After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.

Methods

In a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects.

Results

Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed.

Conclusions

In addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation.

Schmid, Y., Enzler, F., Gasser, P., Grouzmann, E., Preller, K. H., Vollenweider, F. X., … & Liechti, M. E. (2014). Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. Biological psychiatry. https://dx.doi.org/doi:10.1016/j.biopsych.2014.11.015
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A single infusion of ketamine improves depression scores in patients with anxious bipolar depression

November 14, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Objective

Patents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressed patients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine’s ability to decrease symptoms of depression.

Methods

Thirty-six patients with anxious (n = 21) and non-anxious (n = 15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5 mg/kg) over 40 min. Post-hoc analyses compared changes in the Montgomery–Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressed patients with bipolar disorder through 14 days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus a HDRS Anxiety/Somatization Factor score of ≥ 7.

Results

A linear mixed model revealed a significant effect of anxiety group on the MADRS (p = 0.04) and HDRS (p = 0.04). Significant drug effects (all p < 0.001) suggested that both anxious and non-anxious groups had an antidepressant response to ketamine. The drug-by-anxiety interactions were not significant (all p > 0.28).

Conclusions

Both anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest a need for further investigations into ketamine’s novel role in the treatment of anxious bipolar depression.

Ionescu, D. F., Luckenbaugh, D. A., Niciu, M. J., Richards, E. M., & Zarate, C. A. (2014). A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar disorders. https://dx.doi.org/10.1111/bdi.12277

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