Open Label Pilot of Lorcaserin (a serotonin 2C-receptor agonist) for Cannabis Use Disorder.

Background And Objective: Cannabis Use Disorder (CUD) has no FDA approved treatment. Serotonin-2c (5HT2c) agonists have preclinical and human laboratory evidence for potential efficacy for CUD. We assessed the tolerability and effects of lorcaserin (5HT2c agonist) on CUD. Methods: In a 10-week, open label, uncontrolled trial, the tolerability of lorcaserin was tested in outpatients with CUD. Adverse events (AE) were assessed weekly. Cannabis use was assessed twice weekly by the Timeline follow-back and quantitative urine metabolites. Results: 17 participants enrolled, and 14 received medication. Participants' average age was 35 years; majority were male (N=12). The medication was well tolerated in males. There were no serious adverse events (SAE). The most common AE's were headache/migraine (N=4, all females), anorexia (N=3), and irritability (N=2). Participants decreased their frequency of cannabis use significantly (p < 0.001), adjusted for baseline use. By the end of the trial, participants decreased by 1.76 (SE=0.47) cannabis using days/week. Average daily amount of cannabis and urine THC metabolite levels did not change significantly. Conclusions: Lorcaserin was well tolerated in males but not females suggesting possible sex differences. Future trials of other 5HT2c agonists (lorcaserin was withdrawn at the request of the FDA) should consider longer dose titration phases. Trial Registration: NCT02932215.

Sleep and alertness disturbance and substance use disorders: A bi-directional relation.

The majority of the literature describing the relation of sleep/alertness disturbance and substance use disorders (SUD) has focused on the disruptive effects of substances with abuse liability on sleep and alertness. Rarely have studies or literature reviews assessed or discussed how sleep/alertness disturbance affects substance use. This paper focuses on the sleep/alertness disturbance side of the relation. We argue that the relation is bi-directional and review evidence showing that sleep/alertness disturbance affects all phases of the addiction cycle, including the initiation, maintenance and relapse of SUD. We review a variety of substances across all phases of the addiction cycle and conclude sleep/alertness disturbance is a critical factor in both understanding and treating SUD.

A week-long outpatient induction onto XR-naltrexone in patients with opioid use disorder.

BACKGROUND: Extended-release (XR) naltrexone can prevent relapse to opioid use disorder following detoxification. However, one of the barriers to initiating XR-naltrexone is the recommendation for a 7-10-day period of abstinence from opioids prior to the first dose. OBJECTIVES: The current study evaluated the feasibility of an XR-naltrexone induction protocol that can be implemented over 1 week in the outpatient clinic. METHODS: Participants (N = 44) were seen in the clinic daily. On Day 1, after abstaining from opioids for at least 12 h, they received buprenorphine 6-8 mg. Adjunctive medications (clonidine, clonazepam, zolpidem, trazodone, and prochlorperazine) were dispensed on Days 2-5, while ascending oral doses of naltrexone were given on Days 3-5 starting with 1 mg dose. An injection of XR-naltrexone was given on Day 5, 1 h after receiving and tolerating naltrexone 24 mg. RESULTS: Of the 44 participants (38 males), 35 (80%) were heroin users and 9 (20%) used prescription opioids. A total of 26 participants (59%) completed the induction and received their first injection of XR-naltrexone. XR-naltrexone was initiated in 54% (19/35) of heroin users and 78% (7/9) of prescription opioid users. CONCLUSION: The results support the feasibility of a week-long outpatient induction onto XR-naltrexone with ascending doses of naltrexone and standing doses of adjunctive medications. By circumventing the need for a protracted period of abstinence and mitigating the severity of withdrawal symptoms experienced during naltrexone titration, this strategy has the potential to increase patient acceptability and access to relapse prevention treatment with XR-naltrexone.

Uncovering the association between fatigue and fatigability in multiple sclerosis using cognitive control.

BACKGROUND: Fatigue and cognitive dysfunction are two common symptoms experienced by patients with multiple sclerosis (MS). The relationship between subjective and objective fatigue (fatigability) in MS is poorly understood. Cognitive control tasks might be more conducive to fatigability and more likely to show associations between subjective and objective cognitive fatigue in MS. OBJECTIVE: To study the association between objective fatigability, as induced by a cognitive control task called the Blocked Cyclic Naming Task (BCNT), subjective fatigue and baseline cognitive functioning in patients with MS. METHODS: Twenty-one patients with MS completed baseline questions about their disease, the Montreal Cognitive Assessment (MoCA) battery and self-reported questionnaires on trait fatigue, sleep and depression. Disability was captured using the expanded disability status scale (EDSS). Participants then performed the BCNT and were asked about their level of state momentary fatigue before and after the BCNT. The BCNT consists of several blocks of either related or unrelated pictures that participants name as quickly as possible. The pictures cycled 4 times in each block and the difference in the response times (RTs) between related and unrelated blocks was captured. Data were analyzed using repeated measures analysis of variance and Pearson correlations. RESULTS: MS participants' performance declined for the related, but not unrelated blocks. The difference in RTs between related and unrelated conditions increased with repetition across cycles (p < 0.001). Participants also showed objective fatigability with less repetition priming (p = 0.02) in the 4th quarter and with greater differences between related and unrelated conditions in the later part of the task. Objective fatigability was strongly associated with participants' assessment of their level of momentary state fatigue (r = 0.612, p = 0.007). CONCLUSION: Using the appropriate tools, this study showed an association between subjective and objective cognitive fatigue in people with MS. The BCNT and cognitive control are useful tools in assessing patients with MS and should be explored in future, larger studies in this population.

Predictive markers in primary breast cancer compared with lymph node and bloodspread metastases.

High levels of HER2 expression identify those patients who might benefit from treatments that target HER2. Among women with metastatic breast cancer, the predictive markers may be different from the primary tumor. We compared predictive markers: Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2 of primary breast carcinomas with those of lymph node (LN) and blood spread metastases (BM). ER, PR and HER2 status were compared between the primary breast tumor and the LN metastasis and blood spread metastasis. ER, PR and HER2 were performed on primary tumor core biopsies and available FNA cell blocks and on metastatic lesions using FDA approved antibodies and HercepTest (Dako). ER and PR were positive when >/=10%. Her2 was positive (amplified/expressed) when 3+ >30% by immunostain or >2.2 by FISH. Sixty four metastatic breast cancer patients were included in this analysis. Forty-eight patients had LN metastases (35 [73 %] diagnosed by FNA) and twenty seven patients had BM (16 [60 %] diagnosed by FNA). P value was determined comparing primary breast with BM and LN for ER, PR and HER2. ER p values when compared for primary breast with BM and LN were 0.45 and 0.57 respectively, and for PR were 0.31 and 0.06 and for HER2 were 0.45 and 0.07. All three predictive markers are similar in the primary and two metastatic sites (lymph node, bloodspread). Only in primary versus lymph node metastases is there a tendency for PR and HER2 (P values 0.06, 0.07) to be different. For HER2, the majority of lymph node metastases are in cell blocks (FNA), fixed in ethanol rather than formalin, which may have caused false positive HER2 expression.

Ovarian carcinoma associated with pregnancy. A review of 9 cases.

BACKGROUND: The purpose of this study was to review patients with ovarian cancer in pregnancy, the effectiveness of the available methods of treatment and their prognosis. METHODS: A retrospective review of all women diagnosed to have cancer of the ovary associated with pregnancy who delivered at the authors' hospitals between January 1976 and December 2000. The demography, clinical presentation, time and mode of diagnosis, treatment, pregnancy outcome and maternal survival were noted. RESULTS: The incidence of ovarian carcinoma in pregnancy in the series was 0.08/1000 deliveries. Of the 9 patients, 7 had epithelial cancers; 4 serous cystadenocarcinoma, 2 mucinous cystadenocarcinomas and one undifferentiated cancer. One patient each had dysgerminoma and granulosa cell tumor. Six patients were in FIGO stage Ia, one Ic, one IIa. One patient was in stage III. Five patients were treated by unilateral salpingo-oophorectomy during pregnancy. Three patients had total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy followed by chemotherapy. Debulking of the tumor was done in a patient in stage III with subsequent chemotherapy. This patient died 13 months from the time of diagnosis of the tumor. The overall 5-year survival rate in the series was 78% and 100% for stage Ia. CONCLUSIONS: Association of ovarian cancer with pregnancy is a rare occurrence. Early diagnosis and appropriate treatment offers the best prognosis for the patient. The higher survival rates in the series was attributed to a larger number of patients in stage I of the disease and 2 patients with a germ cell tumor and dysgerminoma which have the best prognosis. Aggressive postoperative chemotherapy also contributed to the better outcome.