Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle.

Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control.

Conversion of Cannabidiol Following Oral Administration: Authors' Response to Grotenhermen et al. DOI: 10.1089/can.2016.0036.

In a commentary, Grotenhermen, Russo, and Zuardi questioned not only the clinical relevance but also the conclusions of a recently published study by Merrick et al. on the conversion of cannabidiol (CBD) to delta-8 and delta-9-tetrahydrocannabinol (THC) in simulated gastric fluid. In response, this article aims to provide a thorough review of the and studies of gastric CBD conversion as well as potential consequences resulting from such conversion.

Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid.

In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF).

Microneedle-assisted percutaneous delivery of naltrexone hydrochloride in yucatan minipig: in vitro-in vivo correlation.

Although microneedle-assisted transdermal drug delivery has been the subject of multiple scientific investigations, very few attempts have been made to quantitatively relate in vitro and in vivo permeation. The case of naltrexone hydrochloride is not an exception. In the present study, a pharmacokinetic profile obtained following a "poke and patch" microneedle application method in the Yucatan minipig is reported.

Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans.

Purpose: Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window.

Diclofenac enables prolonged delivery of naltrexone through microneedle-treated skin.

Purpose: The purpose of this study was to determine if non-specific COX inhibition could extend pore lifetime in hairless guinea pigs following microneedle treatment.

Methods: Hairless guinea pigs were treated with microneedle arrays ± daily application of Solaraze® gel (3% diclofenac sodium (non-specific COX inhibitor) and 2.5% hyaluronic acid); transepidermal water loss was utilized to evaluate pore lifetime.

Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs.

Controlled-release delivery of 6-beta-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs.

Human skin permeation of 3-O-alkyl carbamate prodrugs of naltrexone.

N-Monoalkyl and N,N-dialkyl carbamate prodrugs of naltrexone (NTX), an opioid antagonist, were synthesized and their in vitro permeation across human skin was determined. Relevant physicochemical properties were also determined. Most prodrugs exhibited lower melting points, lower aqueous solubilities, and higher oil solubilities than NTX.

Flux across [corrected] microneedle-treated skin is increased by increasing charge of naltrexone and naltrexol in vitro.

Purpose: The purpose of this investigation was to evaluate the in vitro microneedle (MN) enhanced percutaneous absorption of naltrexone hydrochloride salt (NTX x HCl) compared to naltrexone base (NTX) in hairless guinea pig skin (GP) and human abdominal skin. In a second set of experiments, permeability of the major active metabolite 6-beta-naltrexol base (NTXOL) in the primarily unionized (unprotonated) form at pH 8.5 was compared to the ionized form (pH 4.

Microneedles permit transdermal delivery of a skin-impermeant medication to humans.

Drugs with poor oral bioavailability usually are administered by hypodermic injection, which causes pain, poor patient compliance, the need for trained personnel, and risk of infectious disease transmission. Transdermal (TD) delivery provides an excellent alternative, but the barrier of skin's outer stratum corneum (SC) prevents delivery of most drugs. Micrometer-scale microneedles (MNs) have been used to pierce animal and human cadaver skin and thereby enable TD delivery of small molecules, proteins, DNA, and vaccines for systemic action.

Human skin permeation of branched-chain 3-0-alkyl ester and carbonate prodrugs of naltrexone.

Purpose: Physicochemical characterization and in vitro human skin diffusion studies of branched-chain ester and carbonate prodrugs of naltrexone (NTX) were compared and contrasted with straight-chain ester and carbonate NTX prodrugs.

Methods: Human skin permeation rates, thermal parameters, solubilities in mineral oil and buffer, and stabilities in buffer and plasma were determined. Partition coefficients between stratum corneum and vehicle were determined for straight- and branched-chain esters with the same number of carbon atoms.