A cautionary tale of paradox and false positives in cannabidiol research.

Introduction: Decades of research on cannabidiol (CBD) have identified thousands of purported cellular effects, and many of these have been proposed to correlate with a vast therapeutic potential. Yet despite the large volume of findings fueling broad optimism in this regard, few have translated into any demonstrable clinical benefit or even notable side effects. Therein resides the great paradox of CBD: a drug that appears to affect almost everything does not clearly do much of anything in a clinical setting.

Regarding the Mechanisms of Promiscuous Cannabinoid Pharmacology: An Elephant Has Entered the Room.

Decades of research have discovered a broad variety of interesting activities resulting from cannabinoid exposure. Recent investigations of cannabidiol, however, present a potential explanation for these findings, which relies on the nonspecific effects of colloidal dispersions as opposed to those of specific drug interactions with macromolecular targets. This perspective raises the question of how false-positive assay results arising from such colloidal interference may permeate the field of cannabinoid pharmacology.

Practical Considerations of Hypotheses and Evidence in Cannabis Pharmacotherapy: Refining Expectations of Clinical Endocannabinoid Deficiency.

An Industry founded on the promotion of presumed health and wellness benefits of cannabis use continues to grow in the United States, despite the lack of substantial evidence in support of the many claims being made. Several hypotheses exist regarding the role of endocannabinoids in human health and the pertinence of phytocannabinoids as pharmacotherapies for addressing their dysregulation. An opinion is offered regarding the tenuous nature of these assumptions and questions are raised regarding how best to interpret the complex metabolic interplay of the still vaguely defined endocannabinoid system.

The 'entourage effect' or 'hodge-podge hashish': the questionable rebranding, marketing, and expectations of cannabis polypharmacy.

Introduction: The concept of a cannabis 'entourage effect' was first coined as a hypothetical afterthought in 1998. Since then, multiple scientific reviews, lay articles, and marketing campaigns have promoted the effect as a wholly beneficial manifestation of polypharmacy expected to modulate the therapeutic effects of cannabis and its derivatives. There is reason to wonder at the authenticity of such claims.

On healthcare by popular appeal: critical assessment of benefit and risk in cannabidiol based dietary supplements.

: In recent decades, federal legislation in the U.S. has recognized a new paradigm of pharmacotherapy in which ideology and popular demand, as opposed to sound clinical evidence, drives the marketing of ostensible herbal therapeutics as 'dietary supplements'.

Studies of targeting and intracellular trafficking of an anti-androgen doxorubicin-formaldehyde conjugate in PC-3 prostate cancer cells bearing androgen receptor-GFP chimera.

The synthesis of a doxorubicin-formaldehyde conjugate bound to the nonsteroidal anti-androgen cyanonilutamide, via a cleavable tether, and binding of the construct to cell free androgen receptor (AR) as a function of tether design were previously reported. Cyanonilutamide bearing a linear alkyne tether bound to the AR better than other designs. Fluorescence microscopy studies of binding of the lead targeted drug, as well as various tethered cyanonilutamides, to the AR and subsequent trafficking of the resulting AR complex in live PC3 prostate cancer cells transfected with AR-green fluorescent protein (GFP) chimera are now described.

Rational design and synthesis of androgen receptor-targeted nonsteroidal anti-androgen ligands for the tumor-specific delivery of a doxorubicin-formaldehyde conjugate.

The synthesis and preliminary evaluation of a doxorubicin-formaldehyde conjugate tethered to the nonsteroidal antiandrogen, cyanonilutamide (RU 56279), for the treatment of prostate cancer are reported. The relative ability of the targeting group to bind to the human androgen receptor was studied as a function of tether. The tether served to attach the antiandrogen to the doxorubicin-formaldehyde conjugate via an N-Mannich base of a salicylamide derivative.