The endocannabinoid system is expressed in bone, although its role in the regulation of bone growth is controversial. Many studies have examined the effect of endocannabinoids directly on osteoclast function, but few have examined their role in human osteoblast function, which was the aim of the present study. Human osteoblasts were treated from seeding with increasing concentrations of anandamide or 2-arachidonoylglycerol for between 1 and 21 days. Cell proliferation (DNA content) and differentiation (alkaline phosphatase (ALP), collagen and osteocalcin secretion and calcium deposition) were measured. Anandamide and 2-arachidonoylglycerol significantly decreased osteoblast proliferation after 4 days, associated with a concentration-dependent increase in ALP. Inhibition of endocannabinoid degradation enzymes to increase endocannabinoid tone resulted in similar increases in ALP production. 2-arachidonoylglycerol also decreased osteocalcin secretion. After prolonged (21 day) treatment with 2-arachidonoylglycerol, there was a decrease in collagen content, but no change in calcium deposition. Anandamide did not affect collagen or osteocalcin, but reduced calcium deposition. Anandamide increased levels of phosphorylated CREB, ERK 1/2 and JNK, while 2-arachidonoylglycerol increased phosphorylated CREB and Akt. RT-PCR demonstrated the expression of CB2 and TRPV1, but not CB1 in HOBs. Anandamide-induced changes in HOB differentiation were CB1 and CB2-independent and partially reduced by TRPV1 antagonism, and reduced by inhibition of ERK 1/2 and JNK. Our results have demonstrated a clear involvement of anandamide and 2-arachidonoylglycerol in modulating the activity of human osteoblasts, with anandamide increasing early cell differentiation and 2-AG increasing early, but decreasing late osteoblast-specific markers of differentiation.

Background Afghanistan, Colombia and Myanmar are the world’s leading heroin and cocaine producers and have also experienced prolonged periods of armed conflict. The link between armed conflict and drug markets is well established but how conflict impacts on the health and social determinants of people who use drugs is less clear. The aim was to investigate health outcomes and associated factors among people who use illicit drugs in Afghanistan, Colombia and Myanmar. Methods We conducted a systematic review searching Medline, EMBASE, PsychINFO and Global Health databases using terms relating to Afghanistan, Colombia and Myanmar; illicit drug use (all modes of drug administration); health and influencing factors. Quality assessment was assessed with the Newcastle–Ottawa-Scale and papers were analysed narratively. Results 35 studies were included in Afghanistan (n = 15), Colombia (n = 9) and Myanmar (n = 11). Health outcomes focused predominantly on HIV, Hepatitis C (HCV), Hepatitis B and sexually transmitted infections (STIs), with one study looking at human rights violations (defined as maltreatment, abuse and gender inequality). Drug use was predominantly injection of heroin, often alongside use of amphetamines (Myanmar), cocaine and cocaine-based derivatives (Colombia). Only one study measured the effect of a period of conflict suggesting this was linked to increased reporting of symptoms of STIs and sharing of needles/syringes among people who inject drugs. Findings show high levels of external and internal migration, alongside low-income and unemployment across the samples. External displacement was linked to injecting drugs and reduced access to needle/syringe programmes in Afghanistan, while initiation into injecting abroad was associated with increased risk of HCV infection. Few studies focused on gender-based differences or recruited women. Living in more impoverished rural areas was associated with increased risk of HIV infection. Conclusions More research is needed to understand the impact of armed-conflict and drug production on the health of people who use drugs. The immediate scale-up of harm reduction services in these countries is imperative to minimize transmission of HIV/HCV and address harms associated with amphetamine use and other linked health and social care needs that people who use drugs may face.

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