Product labeling accuracy and contamination analysis of commercially available cannabidiol product samples.

Background and objective: Commercially available cannabidiol (CBD) products are increasingly being used for medicinal purposes, including for the treatment of various neurological conditions, but there are growing concerns around adherence to quality control measures that protect consumers. This study was conducted to assess the purity and label accuracy of commercially available CBD products. Methods: Commercially available CBD products were chosen from the open stream of commerce in the United States based on formulations as a tincture, gummy, vape, or topical product. Cannabinoid concentrations were analyzed to verify label accuracy including "full spectrum," "broad spectrum," and "CBD isolate" claims on the product label. Analysis for the presence of contaminants included evaluation for heavy metals, pesticides, and residual solvents. Labeled and actual total amounts of CBD and levels of impurities such as heavy metals, residual solvents, and pesticides were measured. Results: A total of 202 CBD products (100 tinctures, 48 gummies, 34 vape products, and 20 topicals) were chosen to represent a broad sample in the United States. Of the products tested (full spectrum, n = 84; broad spectrum, n = 28; CBD isolate, n = 37), 26% did not meet the definition for product type claimed on the packaging. The majority of products (74%) deviated from their label claim of CBD potency by at least 10%. Heavy metals were detected 52 times across 44 of the 202 products tested, with lead being the most prevalent heavy metal. Residual solvents were detected 446 times across 181 of 202 products, with the highest concentrations reported for hexane, m/p-xylene, methanol, and o-xylene. Of 232 pesticides tested, 26 were found 55 times across 30 products. A total of 3% of heavy metals, 1% of residual solvents, and 1% of pesticides violated >1 regulatory threshold. Discussion: This study demonstrated that the majority of commercially available CBD products tested within the current study are inaccurately labeled. Heavy metals, residual solvents, and pesticides were found in several products, some of which violated regulatory thresholds. Thus, uniform compliance with CBD quality control measures is lacking and raises consumer protection concerns. Improved regulatory oversight of this industry is recommended.

The effect of electroacupuncture on osteosarcoma tumor growth and metastasis: analysis of different treatment regimens.

Osteosarcoma is the most common malignant bone tumor found in children and adolescents and is associated with many complications including cancer pain and metastasis. While cancer patients often seek complementary and alternative medicine (CAM) approaches to treat cancer pain and fatigue or the side effects of chemotherapy and treatment, there is little known about the effect of acupuncture treatment on tumor growth and metastasis. Here we evaluate the effects of six different electroacupuncture (EA) regimens on osteosarcoma tumor growth and metastasis in both male and female mice. The most significant positive effects were observed when EA was applied to the ST-36 acupoint twice weekly (EA-2X/3) beginning at postimplantation day 3 (PID 3). Twice weekly treatment produced robust reductions in tumor growth. Conversely, when EA was applied twice weekly (EA-2X/7), starting at PID 7, there was a significant increase in tumor growth. We further demonstrate that EA-2X/3 treatment elicits significant reductions in tumor lymphatics, vasculature, and innervation. Lastly, EA-2X/3 treatment produced a marked reduction in pulmonary metastasis, thus providing evidence for EA's potential antimetastatic capabilities. Collectively, EA-2X/3 treatment was found to reduce both bone tumor growth and lung metastasis, which may be mediated in part through reductions in tumor-associated vasculature, lymphatics, and innervation.

Testosterone and nucleus accumbens dopamine in the male Syrian hamster.

Most drugs of abuse increase dopamine (DA) in nucleus accumbens (Acb). However, the effects of anabolic androgenic steroids (AAS) on Acb DA have not been examined. We determined the effects of subcutaneous (sc) testosterone (T) on Acb DA in male hamsters. The effects of sc amphetamine were also examined for comparison. In addition, Acb DA was evaluated during intracerebroventricular (ICV) T infusion, designed to mimic T intake during ICV T self-administration in drug-naïve and drug-preexposed animals. Acb DA was measured using in vivo microdialysis and HPLC-EC. T (7.5 or 37.5 mg/kg), amphetamine (1 or 5 mg/kg), or vehicle was injected sc and Acb DA monitored for 4h. In the ICV experiment, T (1 or 2 microg/infusion) or vehicle was infused ICV every 6 min for 4h and Acb DA monitored. ICV T preexposure was accomplished by repeating the same ICV T infusion (1 microg/infusion) daily for 14 days, and T infusion was accompanied by microdialysis on 15th day. Neither sc nor ICV T administration increased Acb DA. At high dose (2 microg/infusion), ICV T decreased Acb DA. Likewise, daily ICV infusion of T for 15 days did not alter Acb DA. In contrast, sc amphetamine significantly increased Acb DA at both doses. Therefore, unlike many drugs of abuse, AAS does not increase Acb DA levels. The reduction in DA at high T doses is likely due to autonomic depressant effects of AAS. We suggest that AAS act via mechanism distinct from those of stimulants, but may share neural substrates with other drugs of abuse.

Chemosensory cues are essential for mating-induced dopamine release in MPOA of male Syrian hamsters.

The medial preoptic area (MPOA) is crucial for male sex behavior. Dopamine (DA) is released in MPOA during copulation, and contributes to the reinforcing effects of mating. The aim of the present study was to identify sensory stimuli responsible for mating-induced DA release. Specifically, we determined if chemosensory cues are essential for mating-induced MPOA DA release using in vivo microdialysis in male Syrian hamsters. Hamsters were used because chemosensory cues from the olfactory mucosa and vomeronasal organ are essential for sexual behavior in this species. Sexually experienced adult male hamsters were implanted with a microdialysis guide cannula over MPOA. At the same time, males received sham olfactory bulbectomy (Sham Bx, n = 11), bilateral bulbectomy (Bibx, n = 6), or unilateral bulbectomy (Ubx) ipsilateral (Ipsi Ubx, n = 9) or contralateral (Contra Ubx, n = 8) to the microdialysis probe. This model takes advantage of the predominantly ipsilateral projections of the olfactory bulbs. Microdialysis samples were collected from the MPOA during baseline, exposure to a receptive female, and after removal of female. Extracellular DA was measured using high-performance liquid chromatography with electrochemical detection. During mating, DA increased in MPOA of Sham Bx males (to 146.7 +/- 17.5% of baseline). Bibx males did not mate, and MPOA DA did not increase (96.1 +/- 15.8% of baseline). Although both groups of Ubx males mated to ejaculation, MPOA DA increased significantly only in Contra Ubx males (to 161.8 +/- 35.3% of baseline), and not in males with Ipsi Ubx (107.6 +/- 11.5% of baseline). The results demonstrate that chemosensory cues are essential for MPOA DA release during mating in male Syrian hamsters.

Testosterone self-administration in female hamsters.

Abuse of anabolic-androgenic steroids (AAS) is a growing public health concern. In addition to their anabolic effects, steroids are also reinforcing as demonstrated by testosterone self-administration in male hamsters. However, steroid use in women lags behind that in men. Are androgens also rewarding in females? We determined if female hamsters voluntarily consume testosterone by intracerebroventricular (i.c.v.) self-administration in an operant chamber. Twelve ovary-intact female hamsters self-administering testosterone (1.0 microg/microl) i.c.v. for 19.1 +/- 2.3 days developed a significant preference (P < 0.05) for the active nose-poke (31.5 +/- 6.1 nose-pokes/4 h) over the inactive nose-poke (12.5 +/- 1.1 nose-pokes/4 h). Operant behavior in females was similar to that reported previously for male hamsters. Estrous cycles became irregular 9.6 +/- 2.3 days after the start of self-administration. Regular cycles resumed 13.7 +/- 2.6 days after testosterone was discontinued. To determine the effect of ovarian steroids on androgen self-administration, females were ovariectomized (OVX) and allowed to self-administer testosterone for 10.8 +/- 0.5 days. Afterwards, estrogen was replaced, and self-administration continued for an additional 9.7 +/- 0.6 days. OVX females maintained their preference for the active (23.9 +/- 7.0 nose-pokes/4 h) over the inactive nose-poke (12.6 +/- 3.4 nose-pokes/4 h, P < 0.05), and estrogen had no effect on responding for androgen (active: 25.8 +/- 6.5 nose-pokes; inactive: 8.2 +/- 2.0 nose-pokes/4 h, P < 0.05). Estrous female hamsters did not show a significant preference for stimulus males or females when mating was blocked, and testosterone self-administration did not alter partner preference. However, activity in the preference chamber predicted subsequent androgen intake (R(2) = 0.66, P < 0.05). These findings are consistent with the idea that anabolic steroids have inhibitory effects on female reproduction. Moreover, they suggest that sex differences in androgen reward do not underlie sex differences in AAS abuse in humans.