Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

Background and ObjectivesBuprenorphine/naloxone has been shown to be effective in the treatment of opioid use disorder. Due to its pharmacological properties, induction can be challenging, time‐consuming, and result in sudden onset of withdrawal symptoms.MethodsRetrospective case series (n = 2).ResultsTwo patients with opioid use disorder were successfully started on buprenorphine/naloxone using a rapid micro‐induction technique that did not cause precipitated withdrawal or require preceding cessation of other opioids.Discussion and ConclusionsThese cases provide an alternative method for starting buprenorphine/naloxone that offers unique benefits compared to protocols previously described in the literature.Scientific SignificanceThis method can be used to minimize barriers to opioid agonist therapy. (Am J Addict 2019;28:262–265)

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Objectives: Alternative transition protocols from methadone to buprenorphine in the treatment of opioid use disorder (OUD) are needed to reduce the risk of precipitated withdrawal and opioid use during induction. Methods: Case report (n = 1). Results: One patient with OUD underwent a rapid microinduction outpatient protocol that did not cause precipitated withdrawal or require preceding taper before cessation of methadone. The induction was carried out safely in the outpatient setting. Conclusions: This report provides a patient-centered approach demonstrating feasibility and cost-effectiveness of rapid transition to buprenorphine in the US outpatient psychiatry setting. Barriers to adherence to opioid agonist therapy may be reduced using this protocol.

Buprenorphine is an effective treatment for chronic pain and may reduce opioid-induced hyperalgesia. However, its pharmacological properties make its induction challenging, timeconsuming, and can precipitate opioid withdrawal. We present the case of a 66-year-old woman with inadequately controlled postoperative pain despite escalating doses of oxycodone and methadone, who was successfully transitioned to buprenorphine/naloxone using a rapid microinduction technique without precipitating opioid withdrawal. Rapid induction provides an alternative method for transitioning patients from other opioids to buprenorphine/naloxone and facilitates transition of patients with chronic pain to buprenorphine therapy within a shorter window compared to currently existing protocols.

BackgroundDiets rich in the n-3 fatty acid alpha-linolenic acid (ALA) have been shown to reduce breast tumor growth, enhance the effectiveness of the HER2-targeted drug trastuzumab (TRAS) and reduce HER2 signaling in mouse models. It is unclear whether this is due to direct effects of ALA or due to its long-chain n-3 fatty acids metabolites including docosahexaenoic acid (DHA).MethodsThe ability of HER2-overexpressing BT-474 human breast cancer cells to convert ALA to long-chain n-3 fatty acids was determined by measurement of phospholipid fatty acids by gas chromatography following treatment with 100 μM ALA. The effects of 96 h treatment with ALA or DHA, at serum levels seen in mice (50–100 μM), alone and combined with TRAS (10 μg/ml), on BT-474 cell growth measured by trypan blue exclusion, apoptosis measured by flow cytometric analysis of Annexin-V/7-AAD stained cells (ALA and TRAS treatment only) and protein biomarkers HER2 signaling measured by western blot were determined.ResultsALA-treated BT-474 cells had higher phospholipid ALA but no increase in downstream n-3 metabolites including DHA. Both ALA and DHA reduced cell growth with and without TRAS. ALA had no effect on apoptosis. ALA and DHA showed opposite effects on Akt and MAPK phosphorylation; ALA increased and DHA decreased phosphorylation.ConclusionsTogether these data suggest that, while both ALA and its DHA metabolite can reduce HER2-overexpressing breast cancer growth with and without TRAS, they demonstrate for the first time that DHA is responsible for the effects of ALA-rich diets on HER2 signaling pathways.

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Background: Due to its unique pharmacologic properties, efficacy as an analgesic, and role as a first-line medication for the treatment of opioid use disorder, sublingual buprenorphine has emerged as a treatment for patients with concurrent chronic pain and opioid use disorders. One challenge to utilizing buprenorphine is that precipitated opioid withdrawal can result if this medication is initiated in the presence of other opiates with lesser binding affinities. Microdosing induction regimens utilize a slower titration to avoid the need for a period of abstinence from other opiates and decrease the risk of precipitated withdrawal. Aims: The aim of this article is to present a case where a standardized micro-dosing induction regimen was used to transition a patient from other opiate analgesia to a sublingual formulation of buprenorphine/naloxone. Methods: This case took place on an inpatient neurosurgical unit of a Canadian tertiary-care city hospital. Written informed consent was collected prior to a detailed chart review. Results: Here we present a case of a postoperative neurosurgical inpatient who was referred to our team for pain management in the context of chronic pain and a past history of opioid use disorder. She was successfully transitioned to buprenorphine/naloxone, replacing all other opioid analgesia, without a period of opioid withdrawal using a micro-dosing induction regimen. Conclusions: Sublingual buprenorphine/naloxone can be safe and effective for treatment of chronic pain, particularly for those with past or current opioid use disorder. Micro-dosing provides a preferable induction strategy for patients who are not able to tolerate the requirement for moderate opioid withdrawal prior to initiation with existing regimens. RÉSUMÉ