Correction: Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects

Breuer, Aviva; Haj, Christeene; Fogaça, Manoela V.; Gomes, Felipe V.; Silva, Nicole Rodrigues da; Pedrazzi, João Francisco Cordeiro; Del‐Bel, Elaine; Hallak, Jaime C.; Crippa, José Alexandre S; Zuardi, Antônio Waldo; Mechoulam, Raphael; Guimarães, Francisco Silveira

doi:10.1371/journal.pone.0162087

Cited by 5 publications

(2 citation statements)

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“…These studies utilize standardized behavioral tests (such as elevated plus maze (EPM) for anxiety-like behavior and forced swim test (FST) for testing depressive-like behavior) to assess changes in symptom severity and activity of drugs. Indeed, fluorinated CBD derivatives showed high potency for behavioral effects in the EPM and FST [ 24 - 26 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

et al. 2020

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Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, ‘cannabis’ is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the “entourage effect” is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.

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Section: Introductionmentioning

confidence: 99%

The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

et al. 2020

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“…To improve the therapeutic effect of (−)-CBD, we modified four distinct regions of the CBD scaffold (Figure ). Utilizing (−)-CBD isolate, we first modified the limonene moiety (Figure , blue) to examine both the necessity of its rigidity and whether or not introduction of hydrogen bond donors and acceptors would vary its activity (JGC4–16,48–50). − We also altered the lipid tail of both (+/−)-CBD (Figure , green) via total synthesis utilizing commercially available starting materials and late-stage diversification (JGC23–47). − We modified the resorcinol ring (Figure , red) to examine the necessity of the phenolic groups (JGC2,3). Finally, we synthesized four diastereomer analogs of CBD (Figure , asterisk) to evaluate the geometric constraints of its binding pockets (JGC17–22) .…”

Section: Resultsmentioning

confidence: 99%

Structure–Activity Relationship Study of Cannabidiol-Based Analogs as Negative Allosteric Modulators of the μ-Opioid Receptor

Bosquez-Berger,

Gudorf,

Kuntz

et al. 2023

J. Med. Chem.

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The US faces an unprecedented surge in fatal drug overdoses. Naloxone, the only antidote for opiate overdose, competes at the mu opioid receptor (μOR) orthosteric site. Naloxone struggles against fentanyl-class synthetic opioids that now cause ∼80% of deaths. Negative allosteric modulators (NAMs) targeting secondary sites may noncompetitively downregulate μOR activation. (−)-Cannabidiol ((−)-CBD) is a candidate μOR NAM. To explore its therapeutic potential, we evaluated the structure–activity relationships among CBD analogs to identify NAMs with increased potency. Using a cyclic AMP assay, we characterize reversal of μOR activation by 15 CBD analogs, several of which proved more potent than (−)-CBD. Comparative docking investigations suggest that potent compounds interact with a putative allosteric pocket to stabilize the inactive μOR conformation. Finally, these compounds enhance naloxone displacement of fentanyl from the orthosteric site. Our results suggest that CBD analogs offer considerable potential for the development of next-generation antidotes for opioid overdose.

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Synthetic, non-intoxicating 8,9-dihydrocannabidiol for the mitigation of seizures

Mascal

Hafezi

Wang

et al. 2019

Sci Rep

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There can be a fine line between therapeutic intervention and substance abuse, and this point is clearly exemplified in herbal cannabis and its products. Therapies involving cannabis have been the treatment of last resort for some cases of refractory epilepsy, and this has been among the strongest medical justifications for legalization of marijuana. In order to circumvent the narcotic effects of Δ 9 -tetrahydrocannabinol (THC), many studies have concentrated on its less intoxicating isomer cannabidiol (CBD). However, CBD, like all natural cannabinoids, is a controlled substance in most countries, and its conversion into THC can be easily performed using common chemicals. We describe here the anticonvulsant properties of 8,9-dihydrocannibidiol (H2CBD), a fully synthetic analogue of CBD that is prepared from inexpensive, non-cannabis derived precursors. H2CBD was found to have effectiveness comparable to CBD both for decreasing the number and reducing the severity of pentylenetetrazole-induced seizures in rats. Finally, H2CBD cannot be converted by any reasonable synthetic route into THC, and thus has the potential to act as a safe, noncontroversial drug for seizure mitigation.

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Correction: Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects

Cited by 5 publications

References 1 publication

The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

Structure–Activity Relationship Study of Cannabidiol-Based Analogs as Negative Allosteric Modulators of the μ-Opioid Receptor

Synthetic, non-intoxicating 8,9-dihydrocannabidiol for the mitigation of seizures

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