Background
Recent research demonstrated the potential of psychedelic drugs as treatment for depression and death-related anxiety and as an enhancement for well-being. While generally positive, ...responses to psychedelic drugs can vary according to traits, setting, and mental state (set) before and during ingestion. Most earlier models explain minimal response variation, primarily related to dosage and trust, but a recent study found that states of surrender and preoccupation at the time of ingestion explained substantial variance in mystical and adverse psilocybin experiences.
Objectives
The current study sought to replicate the previous model, extend the model with additional predictors, and examine the role of mystical experience on positive change.
Method
A hierarchical regression model was created with crowdsourced retrospective data from 183 individuals who had self-administered psilocybin in the past year. Scales explored mental states before, during, and after psilocybin ingestion, relying on open-ended memory prompts at each juncture to trigger recollections. Controlled drug administration was not employed.
Results
This study replicated the previous model, finding a state of surrender before ingestion a key predictor of optimal experience and preoccupation a key predictor of adverse experience. Additional predictors added to the explanatory power for optimal and adverse experience. The model supported the importance of mystical experiences to long-term change.
Conclusion
Mental states of surrender or preoccupation at the time of ingestion explain variance in mystical or adverse psilocybin experiences, and mystical experiences relate to long-term positive change. The capacity to recognize this optimal preparatory mental state may benefit therapeutic use of psilocybin in clinical settings.
A web-based survey on mephedrone Carhart-Harris, R.L; King, L.A; Nutt, D.J
Drug and alcohol dependence,
10/2011, Letnik:
118, Številka:
1
Journal Article
Recenzirano
Abstract Background This study sought to collect information on the former legal-high ‘mephedrone’ using a web-based survey targeted at mephedrone users. Methods The survey was advertised on websites ...frequented by drug users. Individuals were invited to complete the survey if they had taken mephedrone on at least one occasion in the past. Results One thousand and six completed forms were received from declared users, making this the largest survey on mephedrone to date. Conclusion Results showed that mephedrone users consider its effects to compare best with those of MDMA, and while MDMA was considered marginally safer and its effects more pleasurable, mephedrone's appeal lay in its availability, low price and reliable purity.
This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the ...anarchic brain, founded on the principle that-via their entropic effect on spontaneous cortical activity-psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system. We assemble evidence for this model and show how it can explain a broad range of phenomena associated with the psychedelic experience. With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors. We end by discussing further implications of the model, such as that psychedelics can bring about the revision of other heavily weighted high-level priors, not directly related to mental health, such as those underlying partisan and/or overly-confident political, religious, and/or philosophical perspectives. SIGNIFICANCE STATEMENT: Psychedelics are capturing interest, with efforts underway to bring psilocybin therapy to marketing authorisation and legal access within a decade, spearheaded by the findings of a series of phase 2 trials. In this climate, a compelling unified model of
psychedelics alter brain function to alter consciousness would have appeal. Towards this end, we have sought to integrate a leading model of global brain function,
, with an often-cited model of the acute action of psychedelics,
. The resulting synthesis states that psychedelics work to relax high-level priors, sensitising them to liberated bottom-up information flow, which, with the right intention, care provision and context, can help guide and cultivate the revision of entrenched pathological priors.
Rationale
There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in ...psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study.
Objectives
The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD.
Methods
Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5–7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9).
Results
Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions “wonder”, “transcendence”, “power” and “tenderness”.
Conclusions
These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.
Cardiac autonomic modulation and baroreflex sensitivity (BRS) are altered in individuals with hypertension. Aerobic exercise (AE) training has been shown to improve both measures, yet little is known ...about the effects of resistance exercise (RE). The purpose of this study was to examine the heart rate variability (HRV) and BRS following 4 weeks of resistance or aerobic training in a population with borderline high blood pressure (BP). Twenty-nine mild hypertensives were recruited and randomly assigned to 4 weeks of RE or AE training. Before and after training, resting measures of HRV frequencies and BRS were obtained. There was a significant decrease in resting systolic BP for both exercise training modes (RE 136 ± 3.0 pre- to 132 ± 3.4 post-training vs. AE 142 ± 4.0 pre- to 137 ± 3.6 mmHg post-training, P = 0.019). Diastolic BP decreased significantly following both exercise training modes (RE 78 ± 1.31 pre to 74 ± 1.1 post vs. AE 80 ± 1.7 pre to 77 ± 1.6 mmHg post, P = 0.002). A significant time by training mode interaction for low frequency : high frequency (HF) ratio (P = 0.017) with AE decreasing the ratio (275.21 ± 67.28 to 161.26 ± 61.49) and RE increasing this ratio (143.73 ± 65.00 to 227.83 ± 59.41). Natural log-transformed (ln) HRV values showed a time-by-training mode interaction for ln HF (P = 0.05) as ln HF increased (4.7 ± 0.38 to 5.4 ± 0.35 ms²) following AE and decreased (5.98 ± 0.37 to 5.76 ± 0.42 ms²) following RE. BRS increased following aerobic training and decreased after resistance training (6.74 ± 1.2 to 7.94 ± 1.3 and 10.44 ± 1.2 to 9.1 ± 1.2 ms mmHg⁻¹ respectively, P = 0.021). Aerobic exercise improved the autonomic nervous system (increasing vagal tone, reducing sympathovagal balance while increasing BRS) while RE showed no improvements in cardiac autonomic tone and decreased BRS.
Despite the widespread application of drug modelling in psychiatric research, the relative value of different models has never been formally compared in the same analysis. Here we compared the ...effects of five drugs (cannabis, psilocybin, amphetamine, ketamine and alcohol) in relation to psychiatric symptoms in a two-part subjective analysis. In the first part, mental health professionals associated statements referring to specific experiences, for example ‘I don’t bother to get out of bed’, to one or more psychiatric symptom clusters, for example depression and negative psychotic symptoms. This measured the specificity of an experience for a particular disorder. In the second part, individuals with personal experience with each of the above-listed drugs were asked how reliably each drug produced the experiences listed in part 1, both acutely and sub-acutely. Part 1 failed to find any experiences that were specific for negative or cognitive psychotic symptoms over depression. The best model of positive symptoms was psilocybin and the best models overall were the acute alcohol and amphetamine models of mania. These results challenge current assumptions about drug models and motivate further research on this understudied area.
Rationale
Lysergic acid diethylamide (LSD) has a history of use as a psychotherapeutic aid in the treatment of mood disorders and addiction, and it was also explored as an enhancer of mind control.
...Objectives
The present study sought to test the effect of LSD on suggestibility in a modern research study.
Methods
Ten healthy volunteers were administered with intravenous (i.v.) LSD (40–80 μg) in a within-subject placebo-controlled design. Suggestibility and cued mental imagery were assessed using the Creative Imagination Scale (CIS) and a mental imagery test (MIT). CIS and MIT items were split into two versions (A and B), balanced for ‘efficacy’ (i.e. A≈B) and counterbalanced across conditions (i.e. 50 % completed version ‘A’ under LSD). The MIT and CIS were issued 110 and 140 min, respectively, post-infusion, corresponding with the peak drug effects.
Results
Volunteers gave significantly higher ratings for the CIS (
p
= 0.018), but not the MIT (
p
= 0.11), after LSD than placebo. The magnitude of suggestibility enhancement under LSD was positively correlated with trait conscientiousness measured at baseline (
p
= 0.0005).
Conclusions
These results imply that the influence of suggestion is enhanced by LSD. Enhanced suggestibility under LSD may have implications for its use as an adjunct to psychotherapy, where suggestibility plays a major role. That cued imagery was unaffected by LSD implies that suggestions must be of a sufficient duration and level of detail to be enhanced by the drug. The results also imply that individuals with high trait conscientiousness are especially sensitive to the suggestibility-enhancing effects of LSD.
We investigated a novel treatment paradigm for developing functional ambulation in wheelchair-dependent individuals with chronic, incomplete spinal-cord injury. By coordinating epidural stimulation ...of the dorsal structures of the spinal cord with partial weight bearing treadmill therapy, we observed improvement in treadmill and over-ground ambulation in an individual with chronic incomplete tetraplegia. The application of partial weight-bearing therapy alone was not sufficient to achieve functional ambulation over ground, though treadmill ambulation improved significantly. Combining epidural spinal-cord stimulation (ESCS, T/sub 10/-T/sub 12/ vertebral levels) with partial weight-bearing therapy resulted in further improvement during treadmill ambulation. Moreover, the combination of therapies facilitated the transfer of the learned gait into over ground ambulation. Performance improvements were elicited by applying continuous, charge-balanced, monophasic pulse trains at a frequency of 40-60 Hz, a pulse duration of 800 /spl mu/s, and an amplitude determined by the midpoint (50%) between the sensory and motor threshold values. The participant initially reported a reduction in sense of effort for over ground walking from 8/10 to 3/10 (Borg scale), and was able to double his walking speed. After several weeks of over ground training, he reached maximum walking speeds of 0.35 m/s, and was able to ambulate over 325 m. We propose that ESCS facilitated locomotor recovery in this patient by augmenting the use-dependent plasticity created by partial weight bearing therapy. Confirmation of these promising results in a controlled study of groups of spinal-cord-injured subjects is warranted.
This study tested the hypothesis that limb venous responses to baroreceptor unloading are altered in individuals with high blood pressure (HBP) compared with normotensive (NT) controls. Calf venous ...compliance was assessed in 20 subjects with prehypertension and stage-1 hypertension (mean arterial pressure, MAP: 104±1 mm Hg) and 13 NT controls (MAP: 86±2 mm Hg) at baseline and during lower body negative pressure (LBNP), using venous occlusion plethysmography. Baroreflex sensitivity (BRS) was measured using the sequence technique and total peripheral resistance (TPR) was estimated from finger plethysmography. Baseline venous compliance was not different between groups, but the HBP group had lower baseline lnBRS (2.22±0.14 vs 2.7±0.18 ms mm Hg(-1)) and greater baseline TPR (3828±138 vs 3250±111 dyn sec(-1) cm(-5) m(2), P<0.05). Calf venous compliance was reduced in response to LBNP only in the NT group (P<0.05). The HBP group had a greater increase in TPR (ΔTPR) compared with the NT group (+1649±335 vs +718±196 dyn sec(-1) cm(-5) m(2), P<0.05). In conclusion, the early stages of hypertension are characterized by an attenuated venoconstrictor response to baroreceptor unloading, which may compensate for an exaggerated vasoconstrictor response and protect against further increases in blood pressure.
Objective: To examine the responsiveness of cardiac autonomic function and baroreflex sensitivity (BRS) to exercise training in obese individuals without (OB) and with type 2 diabetes (ObT2D). ...Design: Subjects were tested in the supine position and in response to a sympathetic challenge before and after a 16-week aerobic training program. All testing was conducted in the morning following a 12-h fast. Subjects: A total of 34 OB and 22 ObT2D men and women (40–60 years of age) were studied. Measurements: Heart rate variability (HRV) was measured at rest via continuous ECG (spectral analysis with the autoregressive approach) and in response to upright tilt. The dynamics of heart rate complexity were analyzed with sample entropy and Lempel–Ziv entropy, and BRS was determined via the sequence technique. Subjects were aerobically trained 4 times per week for 30–45 min for 16 weeks. Results: Resting HR decreased and total power (lnTP, ms2) of HRV increased in response to exercise training (P<0.05). High frequency power (lnHF) increased in OB subjects but not in OBT2D, and no changes occurred in ln low frequency/HF power with training. Upright tilt decreased lnTP and lnHF and increased LF/HF (P<0.01) but there were no group differences in the magnitude of these changes nor were they altered with training in either group. Tilt also decreased complexity (sample entropy and Lempel–Ziv entropy; P<0.001), but there was no group or training effect on complexity. BRS decreased with upright tilt (P<0.01) but did not change with training. Compared to OB subjects the ObT2D had less tilt-induced changes in BRS. Conclusion: Exercise training improved HRV and parasympathetic modulation (lnHF) in OB subjects but not in ObT2D, indicating plasticity in the autonomic nervous system in response to this weight-neutral exercise program only in the absence of diabetes. HR complexity and BRS were not altered by 16 weeks of training in either OB or ObT2D individuals.
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