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Analyze and summarize the key concerns surrounding synthetic cannabinoids, including their pharmacology, toxicology, and public health impact. Address the following key areas:
1. The history and development of synthetic cannabinoids, from JWH-018 to modern variants like MDMB-4en-PINACA.
2. Mechanisms of action and potency differences compared to Δ9-THC, including CB1 and CB2 receptor binding.
3. Toxicity profiles and severe health outcomes, including seizures, psychosis, kidney injury (e.g., XLR11), and coagulopathy.
4. The legal and forensic challenges of regulating synthetic cannabinoids, including analog laws and evolving chemical modifications.
5. The emergence of "zombie-like" reactions, mass poisoning events, and the role of synthetic cannabinoids in correctional facilities.
6. Detection challenges, including limitations of standard drug screenings and the need for advanced analytical methods (e.g., LC-MS).
Create a decision-support framework for healthcare providers and policymakers, including:
- Clinical guidelines for managing acute toxicity and agitation.
- Public health strategies to track and mitigate synthetic cannabinoid outbreaks.
- Considerations for forensic toxicology and legislative approaches.
- Risk communication strategies for patients and at-risk communities.
Highlight cost considerations, legal complexities, and global trends in synthetic cannabinoid use.