In Colorado, for example, the following conditions are state-approved for medical marijuana treatment:

• Cachexia (a condition typically caused by a disease like cancer or AIDS that causes significant weight loss, including muscle loss)
• Cancer
• Glaucoma
• HIV or AIDS
• Persistent muscle spasms
• Seizures
• Severe pain
• Post Traumatic Stress Disorder

Notice anything about that list? Except for PTSD, all of those conditions are primarily physical. 

The relationship between mental health and cannabis use is less clear. The U.S. drug war and decades of misinformation have biased the perception of cannabis use in mainstream medicine and culture.

Is Cannabis an Effective Treatment for Depression?

Thanks to nearly a century of federal cannabis prohibition making most plant studies illegal, there’s a lot about the cannabis plant that we just don’t know.

Study after study shows a correlation between cannabis use and depression, though prohibitionists or federal organizations sometimes use them to discourage cannabis use.

However, as more scientific studies are released and peer-reviewed by unbiased sources, it’s becoming increasingly clear that cannabis may be an effective treatment for the 280 million people in the world who suffer from depression.

Anecdotally, you can look at a longstanding cannabis review site like Leafly.com to see their database includes thousands of strains that users say positively affect depression and anxiety. Scientifically, recent studies released in The Journal of Biology and Medicine and Journal of Affective Disorders found that cannabis use provided great relief to those suffering from depression. 

There’s still plenty of work needed to get to the bottom of marijuana’s actual effects. But based on what we know now, here are five cannabis strains likely to help with symptoms associated with depression—like sadness, insomnia, a lack of energy, low concentration, and appetite loss.

Gelato

Cannabis enthusiasts prize the Gelato strain for its THC rate of 17% and uplifting effects. More than 2,000 people have ranked the strain at Leafly.com’s strain database—with “euphoric,” “aroused,” and “happy” being the top three good feelings they associate with it. 

About a quarter of Leafly’s reviewers said it aids in their depression (24%) and anxiety (26%), while 27% told the site that it’s a good destresser.

Photo: MmeEmil via gettyimages.com

Sherbert

If feeling relaxed, happy, and giggly sounds like a good alternative to your current mood, you’ll want to hit up your nearest dispensary for the Sherbert strain. 

“This strain exhibits powerful, full-body effects that are elevated by a jolt of cerebral energy and carefree state of mind,” Leafly’s in-house strain reviewers say. Its 18% THC rate “makes it an ideal choice for medical marijuana patients seeking relief from symptoms associated with stress, tension and mood disorders.”

Twenty-seven percent of users told Leafly that it helped with their anxiety and depression, respectively, while a whopping 35% said it’s a good stress reliever.

Thin Mint

Thirty percent of Leafly’s users told the company that the Thin Mint strain aids their depression, while 35% said it is a good destresser and 26% said it helps with pain—that’s a medical trifecta. It’s also a trifecta in a different sense, as the strain itself is a cross between sativa Durban Poison, indica OG Kush, and hybrid strain GSC (“Girl Scout Cookie”).

“Uplifted,” “euphoric,” and “relaxed” were users’ three highest-ranked feelings.

Dosidos

If you think you’re noticing a food theme here when it comes to strain names, welcome to the world of cannabis! And let’s talk about eating. Of course, cannabis is famous for its “munchy” effects, but some strains are more potent than others when creating an appetite. 

And being that a lack of appetite can be a sign of depression, what better solution than a strain known for making people hungry? And when “sleepy” and “relaxed” are the other two highest-ranking feelings in the Leafly database, it must be time to grab yourself an eighth of Dosidos.

Skunkberry

No mood-altering list of cannabis strains would be complete without a skunk on it. Yes, the skunk strains are known for smelling like, well, a skunk. They’re also famous for their euphoric and simultaneously pain-relieving high. 

At Leafly’s database, “relaxed,” “euphoric,” and “happy” were the highest-ranked feelings for the Skunkberry strain. About a third of reviewers told the website that Skunkberry helps with pain, stress, and depression. 

The next time you’re feeling a bit down, you might find some relief in alleviating your depression symptoms with one of these top-rated strains.

Lead drug candidate has shown superior and longer-lasting lowering of intraocular pressure, a risk factor associated with glaucoma, in preclinical studies

San Diego, California–(Newsfile Corp. – June 30, 2022) – Skye Bioscience, Inc. (OTCQB: SKYE) (“Skye” or the “Company”), a pharmaceutical company developing a proprietary, synthetic cannabinoid derivative to treat glaucoma, has received regulatory approval to begin its first-in-human Phase 1 clinical study of SBI-100 Ophthalmic Emulsion (“SBI-100 OE”) from the Australian Human Research Ethics Committee (“HREC”). SBI-100 OE is a patented drug representing a new class of therapeutics to potentially treat glaucoma.

The primary endpoints for this randomized, double-masked, placebo-controlled Phase 1 study of SBI-100 OE are an assessment of safety and tolerability of the drug in healthy volunteers. The secondary endpoint is an assessment of pharmacokinetics. The study will also measure changes to intraocular pressure. A total of 48 subjects will be administered SBI-100 OE or placebo in single ascending dose (SAD) and multiple ascending dose (MAD) arms. Preliminary top-line data is expected in Q4 and final data in Q1 of 2023.

In the study, each arm will consist of three cohorts of eight subjects, six receiving SBI-100 OE and two receiving placebo. In the SAD arm, each subject will be administered a single 35uL drop to one study eye of placebo or SBI-100 OE at concentrations of 0.5%, 1.0% and 2.0% of active drug in cohorts one, two, and three, respectively. In the MAD arm, each subject will receive two drops per day over five days using the respective dose levels of the SAD arm. A Safety Review Committee will monitor the study and review safety data before approving escalation to the next cohort.

“After submitting our clinical trial protocol to HREC in March, we are pleased to receive their approval and look forward to assessing SBI-100 Ophthalmic Emulsion for the first time in humans,” said Tu Diep, Chief Development Officer of Skye. “Decades of research have established the role of cannabinoid receptor type 1 (CB1R) in lowering IOP, however, there has been no CB1R agonist therapeutic agent approved by a regulatory agency to treat glaucoma. No other company has methodically created a patented molecule and proprietary formulation – representing a new class of therapeutic drug – to improve the inherent positive attributes of natural cannabinoids while limiting potentially negative systemic effects, and with the goal of enhancing the treatment of glaucoma beyond today’s approved drugs.

“Achieving these goals is Skye’s focus. We have not only created a drug with this ambition but we have also navigated the complexities of synthetic manufacturing and conducted extensive preclinical assessments, and now we are embracing the rigors of the clinical and regulatory processes to validate our drug.”

The Phase 1 study will be conducted in the clinical trial facility of CMAX Clinical Research in Adelaide, Australia (“CMAX”). Conducting the Phase 1 clinical study in Australia qualifies Skye to receive a tax credit of up to 43.5%.

Next Steps

• Submission of Clinical Trial Notification to Australian Therapeutic Goods Administration. This submission is prepared and will be filed now that HREC approval has been obtained.

• Site visit and training. Skye will train the study investigators and CMAX’s clinical study staff on the clinical protocol and procedures and ensure that the pharmacy understands how to appropriately handle the drug formulation.

• Clinical trial material (CTM) production. The manufacturing process of SBI-100 OE requires very specific and specialized equipment, consumables and excipients that cannot be easily substituted. Global supply chain constraints delayed or limited access to certain components of the manufacturing process and delayed CTM production, which was originally scheduled to be completed in early June. We are working with our contract manufacturer, Pharmaceutics International Inc., to finalize logistical and scheduling details. We expect to complete Phase 1 CTM production in July.

• Secure DEA export license and deliver CTM to Australia. Skye has secured the import license required for a controlled substance from the Australian Department of Health. We require an export license from the U.S. Drug Enforcement Agency but must complete CTM production before submitting our application. There can be variability in the timing of the DEA’s review and issue of an export license. We do not expect to receive this license earlier than August, after which delivery of drug product to Australia will be expedited.

• Subject screening, enrollment, and first dosing. Recruitment of study participants will begin after the prior listed steps are substantially completed, since subjects must be administered drug within 28 days of enrollment. Taking into account the listed variables, Skye is aiming to dose the first subject in August.

• Reporting of study data. Skye expects to report preliminary topline data in Q4 2022, with final data to be reported in Q1 2023.

“Glaucoma is still an inadequately treated disease that has lacked pharmacological innovation for decades. There is a need for new classes of therapeutics with differentiated mechanisms of action and we have strong conviction in the potential of our novel drug based on relevant independent research and our preclinical data,” said Punit Dhillon, CEO and Chair of Skye. “This study will be the first time a novel cannabinoid prodrug will be topically delivered into human’s eyes using a nanoemulsion formulation, and marks an important step in the development of SBI-100 Ophthalmic Emulsion to demonstrate the safety of this approach. Importantly, this study may also provide initial insights into this drug’s effect on IOP.

“In parallel, we aim to submit an investigational new drug (IND) application, which is not dependent upon Phase 1 data, with the FDA by year-end for our planned US-based Phase 2 in 2023 to assess efficacy and safety in patients with glaucoma.”

About SBI-100 Ophthalmic Emulsion
Increased intraocular pressure (IOP) is a key risk factor in the progression of glaucoma. The first observations that consuming cannabis lowered IOP in humans took place in the early 1970s, which led to a significant amount of research on the effects of cannabinoids in the eye. Independent studies demonstrated that activation of the cannabinoid receptor-type 1 (CB1R) in ocular tissue mediates IOP-lowering. However, no cannabinoid-related drug has been approved for clinical use in the eye due primarily to the shortcomings of current delivery methods of CB1R agonists to the eye in a therapeutically beneficial dose. When cannabinoids are administered systemically they can lower IOP but also result in undesirable psychotropic effects. Alternatively, extracted natural cannabinoids delivered topically as an eye drop do not penetrate ocular tissue well enough to effectively lower IOP due to the lipophilic, or oily, properties of natural cannabinoids and the aqueous, or watery, surface of the eye.

To address these challenges, Skye developed SBI-100 OE, a proprietary, synthetic cannabinoid derivative possessing a novel molecular structure and formulation that was rationally designed to enable better penetration of ocular tissue and effective topical delivery of a CB1R agonist. In preclinical studies involving three different species, a nanoemulsion formulation of the drug applied topically to the eye resulted in enhanced therapeutic efficacy and duration of response in lowering IOP. Importantly these studies also demonstrated advantages compared to today’s standard of care and, if clinically validated in subsequent efficacy studies, may provide a suitable therapeutic window to be a new class of medicine for glaucoma.

About Skye Bioscience
Skye Bioscience is a pharmaceutical company unlocking the potential of cannabinoids through the development of its proprietary cannabinoid derivatives to treat diseases with significant unmet needs. The company’s lead program, SBI-100 OE, is focused on developing a treatment for glaucoma, the world’s leading cause of irreversible blindness. For more information, please visit: www.skyebioscience.com.

CONTACT
Investor Relations
Email: [email protected]
Phone: (858) 410-0266

FORWARD-LOOKING STATEMENTS
This letter contains forward-looking statements, including statements regarding our product development, business strategy, the timing of clinical trials, and commercialization of cannabinoid-derived therapeutics. Such statements and other statements in this press release that are not descriptions of historical facts are forward-looking statements that are based on management’s current expectations and assumptions and are subject to risks and uncertainties. If such risks or uncertainties materialize or such assumptions prove incorrect, our business, operating results, financial condition, and stock price could be materially negatively affected. In some cases, forward-looking statements can be identified by terminology including “anticipated,” “plans,” “goal,” “focus,” “aims,” “intends,” “believes,” “can,” “could,” “challenge,” “predictable,” “will,” “would,” “may” or the negative of these terms or other comparable terminology. We operate in a rapidly changing environment, and new risks emerge from time to time. As a result, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements the Company may make. Risks and uncertainties that may cause actual results to differ materially include, among others, our capital resources, uncertainty regarding the results of future testing and development efforts and other risks that are described in the Risk Factors section of Skye’s most recent annual or quarterly report filed with the Securities and Exchange Commission. Except as expressly required by law, Skye disclaims any intent or obligation to update these forward-looking statements.

This article was published by CFN Enterprises Inc. (OTCQB: CNFN), owner and operator of CFN Media, the industry’s leading agency and digital financial media network dedicated to the burgeoning CBD and legal cannabis industries. Call +1 (833) 420-CNFN for more information.

About Ryan Allway

Mr. Allway has over a decade of experience in the financial markets as both a private investor and financial journalist. He has been actively involved in the cannabis industry since its inception, covering public and private companies.

• Prototype medical device engineered to deliver sustained, sub-psychedelic quantities of candidate DMT-analogues
• In vitro, time dependent drug elution profile evaluated for three candidate molecules
• Biocompatibility of drug-loaded medical device demonstrates cell-based safety at doses anticipated to be within therapeutic range
• Current results provide Company with refined focus for two candidate molecules

Toronto, Ontario–(Newsfile Corp. – April 7, 2022) – PharmaDrug Inc. (CSE: PHRX) (OTCQB: LMLLF) (“PharmaDrug” or the “Company“), a specialty pharmaceutical company focused on the research, development and commercialization of controlled-substances and natural medicines such as psychedelics, cannabis and naturally-derived approved drugs, is pleased to announce that in collaboration with the Terasaki Institute for Biomedical Innovation (TIBI), it has successfully completed fabrication of a novel medical device capable of delivering sustained, low (sub-psychedelic) quantities of their undisclosed tryptamine-based pharmaceutical to the front of the eye; the intended purpose of which is to potentially lower intraocular pressure (IOP) in patients suffering from glaucoma. Additionally, a head-to-head drug elution study of the Company’s three undisclosed DMT-analogue candidates has now been completed and supportive cell-based biocompatibility has been examined for all three candidate molecules. Future in vivo efficacy testing in an accepted model of primary open angle glaucoma (POAG) is currently being planned with the goal of providing all necessary support to file an investigative new drug (IND) application with the United States Food and Drug Administration (the “FDA“) to conduct clinical studies.

Paul Van Slyke, CSO of PharmaDrug commented, “We are excited to announce that our recently fabricated proprietary medical device, designed to deliver controlled release of tryptamine-based pharmaceutical agents, has now progressed from the concept stage into a functioning prototype. Drug release rates were successfully characterized for each of the candidates under evaluation and as such, the current studies provide the Company with the critical data necessary to fine-tune fabrication efforts while also facilitating informed design for its future IND-enabling efficacy studies which will use a well accepted animal model of glaucoma”.

The aim of PharmaDrug’s DMT-analogue research program in ocular health is to develop suitable prototype medical devices capable of sustained ocular drug-delivery while also confirming efficacy, biocompatibility and stability of its candidate molecules in models of elevated IOP. Previous press releases (Feb 23, 2022, and Dec 13, Nov 5, Aug 5, 2021) have provided updates on in vitro potency, surrogate markers of efficacy and safety/toxicity. With today’s announcement the Company is pleased to deliver on several additional key objectives-namely, fabrication of its drug eluting medical device and in vitro biocompatibility test results. The research program scope currently underway includes full establishment and demonstration of candidate molecule loading capacity, release rate evaluations for conjugated materials as well as model organism testing to support an IND application with the FDA in the future.

The Company has now completed fabrication and initial testing of its novel medical device designed to deliver therapeutic quantities of its DMT-analogues to the front of the eye. Specifically, drug-loaded medical device prototypes were suspended in a biological solution meant to mimic the somewhat harsh environment of the eye. Samples, maintained at body temperature were removed at defined periods of time over sixteen days and were quantified to determine concentration and rate of drug elution for each of the Company’s three candidate molecules. The stability of one of the candidate molecules did not meet minimal necessary criteria and has now been eliminated from further consideration. The remaining two DMT-analogues displayed suitable 2-week provisional stability and elution characteristics that support further evaluation and optimization. One candidate molecule/medical device in particular, displayed a consistent drug elution profile from days 2-16 (end of study) suggesting that drug delivery of greater than two weeks may be possible. The biocompatibility of drug-loaded medical devices was examined by way of monitoring cell proliferation and live/dead staining on human ciliary muscle cells over time. Concentrations expected to be within the therapeutic range were found to not statistically impact cell viability for any of the drug-loaded medical devices.

Test article potency was previously evaluated using an in vitro calcium mobilization assay on trabecular meshwork cells; a cell type known to be critically important in the maintenance of healthy IOP. Calcium mobilization is understood to provoke cellular contraction, and specifically in the case of trabecular meshwork cells, is thought to contribute to the maintenance of healthy IOP by channeling aqueous humor away from the front of the eye. Test articles were found to activate calcium mobilization, to levels that were comparable or greater than the experimental positive control, ionomycin. The Company’s test articles were also examined for in vitro toxicity and were found to be non-toxic to trabecular meshwork cells at concentrations expected to be used in treatment for various eye diseases. Collectively the results of the above studies will be used to select a lead development candidate that will be taken forward into in vivo efficacy models for eye diseases, including glaucoma.

The Need for Improved Medications to Treat Primary Open Angle Glaucoma

Glaucoma is a disorder of the optic nerve that results in irreversible vision loss and is the second leading cause of blindness in the world, according to the World Health Organization. Glaucoma impacts more than 2.7 million people aged 40 or older in the United States and current treatments are known to have poor rates of compliance of up to 80% of patients. The global market for glaucoma was estimated by Market Scope at $4.8 billion in 2019 with the U.S. market representing $1.9 billion. Although the exact etiology of primary open angle glaucoma remains poorly understood, and may be variable across patient subsets, it is generally accepted that the observed increase in IOP correlates with progressive vision loss¹. Current treatments for POAG primarily consist of eye drops that can be grouped into three main categories: prostaglandin analogues, carbonic anhydrous inhibitors, and alpha-2 agonists. While these approaches usually provide partial improvement, they often result in side effects such as redness and stinging and require multiple daily applications; all of which diminish patient compliance. Tryptamines, including DMT-analogues are thought to work in a completely distinct way to lower IOP and as such potentially embody a new class of glaucoma medications that may be used alone, or in combination with already approved medications. The Company’s streamlined focus on two highly promising, undisclosed tryptamines as a potential therapeutic solution in treating glaucoma represents a potential paradigm shift.

Modulating the serotonin receptor pathway to improve glaucoma outcomes

Key regions of the eye that regulate fluid dynamics, including maintenance of healthy IOP, are known to be richly decorated with various serotonin receptor family members. Previous research has highlighted the role of serotonin receptor signaling in the regulation of IOP^2-5. Tryptamines, often hallucinogenic above certain threshold concentrations, constitute a large collection of molecules that selectively act on multiple different serotonin receptors including 5-HT1A and 5-HT2A. Topical application of several different tryptamines have shown early promise in preclinical models of elevated IOP, however formulation, delivery, the potential for undesirable hallucinogenic side effects, and the controlled substances act of 1970 have all contributed to a lack of development of tryptamines to treat this serious threat to vision.

About Terasaki Institute for Biomedical Innovation

The Terasaki Institute for Biomedical Innovation is a biotechnology institute which develops medical devices and cutting-edge protocols for a variety of diagnostic, monitoring and treatment applications. Their research platforms include work in biomaterials, cellular and tissue engineering, wearable biosensors and organs-on-a-chip, with specific expertise in novel polymer development.

About PharmaDrug Inc.

PharmaDrug is a specialty pharmaceutical company focused on the research, development and commercialization of controlled-substances and natural medicines such as psychedelics, cannabis and naturally-derived approved drugs. PharmaDrug owns 100% of Pharmadrug Production GmbH (“Pharmadrug Production”), a German medical cannabis distributor, with a Schedule I European Union narcotics license and German EuGMP certification allowing for the importation and distribution of medical cannabis to pharmacies in Germany and throughout the European Union. PharmaDrug owns 100% Sairiyo Therapeutics (“Sairiyo”), a biotech company that specializes in researching and reformulating established natural medicines with a goal of bringing them through clinical trials and the associated regulatory approval process in the US and Europe. Sairiyo is currently developing its patented reformulation of cepharanthine, a drug that has shown substantial third party validated potential for the treatment of infectious disease and rare cancers. Sairiyo is also conducting R&D in the psychedelics space for the treatment of non-neuropsychiatric conditions. The Company also owns 100% of Super Smart, a company building a vertically integrated retail business with the goal to elevate the use of functional mushrooms, and psilocybin mushrooms where federally legal, as natural based medicines.

For further information, please contact:

Daniel Cohen, Chairman and CEO
[email protected]
(647) 202-124

Caution Regarding Forward-Looking Information:

THE CANADIAN SECURITIES EXCHANGE HAS NOT REVIEWED NOR DOES IT ACCEPT RESPONSIBILITY FOR THE ADEQUACY OR ACCURACY OF THIS RELEASE.

This press release contains “forward-looking information” within the meaning of applicable securities legislation. All statements, other than statements of historical fact, included herein are forward-looking information. Generally, forward-looking information may be identified by the use of forward-looking terminology such as “plans”, “expects” or “does not expect”, “proposed”, “is expected”, “budgets”, “scheduled”, “estimates”, “forecasts”, “intends”, “anticipates” or “does not anticipate”, or “believes”, or variations of such words and phrases, or by the use of words or phrases which state that certain actions, events or results may, could, would, or might occur or be achieved. In particular, this press release contains forward-looking information in relation to: future in vivo efficacy testing in an accepted model of primary open angle glaucoma (POAG), the ability to complete the required studies and obtain regulatory approval, and the impact the Company’s potential products will have on treating glaucoma. This forward-looking information reflects the Company’s current beliefs and is based on information currently available to the Company and on assumptions the Company believes are reasonable. These assumptions include, but are not limited to the ability of the Company to successfully execute on its plans for the Company and its affiliated entities; the ability to obtain required regulatory approvals and the Company’s continued response and ability to navigate the COVID-19 pandemic being consistent with, or better than, its ability and response to date.

Forward-looking information is subject to known and unknown risks, uncertainties and other factors that may cause the actual results, level of activity, performance or achievements of the Company to be materially different from those expressed or implied by such forward-looking information. Such risks and other factors may include, but are not limited to: general business, economic, competitive, political and social uncertainties; general capital market conditions and market prices for securities; the actual results of the Company’s future operations; competition; changes in legislation affecting the Company; the ability to obtain and maintain required permits and approvals, the timing and availability of external financing on acceptable terms; lack of qualified, skilled labour or loss of key individuals; risks related to the COVID-19 pandemic including various recommendations, orders and measures of governmental authorities to try to limit the pandemic, including travel restrictions, border closures, non-essential business closures, service disruptions, quarantines, self-isolations, shelters-in-place and social distancing, disruptions to markets, economic activity, financing, supply chains and sales channels, and a deterioration of general economic conditions; and a deterioration of financial markets that could limit the Company’s ability to obtain external financing.

A description of additional risk factors that may cause actual results to differ materially from forward-looking information can be found in the Company’s disclosure documents on the SEDAR website at www.sedar.com. Although the Company has attempted to identify important factors that could cause actual results to differ materially from those contained in forward-looking information, there may be other factors that cause results not to be as anticipated, estimated or intended. Accordingly, readers should not place undue reliance on forward-looking information. Readers are cautioned that the foregoing list of factors is not exhaustive. Readers are further cautioned not to place undue reliance on forward-looking information as there can be no assurance that the plans, intentions or expectations upon which they are placed will occur. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated.

The Company’s securities have not been registered under the U.S. Securities Act of 1933, as amended (the “U.S. Securities Act”), or applicable state securities laws, and may not be offered or sold to, or for the account or benefit of, persons in the United States or “U.S. Persons”, as such term is defined in Regulations under the U.S. Securities Act, absent registration or an applicable exemption from such registration requirements. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the securities in the United States or any jurisdiction in which such offer, solicitation or sale would be unlawful.

Forward-looking information contained in this press release is expressly qualified by this cautionary statement. The forward-looking information contained in this press release represents the expectations of the Company as of the date of this press release and, accordingly, are subject to change after such date. However, the Company expressly disclaims any intention or obligation to update or revise any forward-looking information, whether as a result of new information, future events or otherwise, except as expressly required by applicable securities law.

References:

1. Weinreb RN, Leung CK, Crowston JG, Medeiros FA, Friedman DS, Wiggs JL, Martin KR. Primary open-angle glaucoma. Nat Rev Dis Primers. 2016 Sep 22;2:16067. doi: 10.1038/nrdp.2016.67. PMID: 27654570.
2. May JA, McLaughlin MA, Sharif NA, Hellberg MR, Dean TR. Evaluation of the ocular hypotensive response of serotonin 5-HT1A and 5-HT2 receptor ligands in conscious ocular hypertensive cynomolgus monkeys. J Pharmacol Exp Ther. 2003 Jul;306(1):301-9. doi: 10.1124/jpet.103.049528. Epub 2003 Apr 3. PMID: 12676887.
3. Sharif NA. Serotonin-2 receptor agonists as novel ocular hypotensive agents and their cellular and molecular mechanisms of action. Curr Drug Targets. 2010 Aug;11(8):978-93. doi: 10.2174/138945010791591278. PMID: 20426763.
4. Najam A Sharif & Jesse A May (2011) Potential for serotonergic agents to treat elevated intraocular pressure and glaucoma: focus on 5-HT2 receptor agonists, Expert Review of Ophthalmology, 6:1, 105-120, DOI: 10.1586/eop.10.69
5. Sharif NA, McLaughlin MA, Kelly CR. AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist. J Ocul Pharmacol Ther. 2007 Feb;23(1):1-13. doi: 10.1089/jop.2006.0093. PMID: 17341144.

This article was published by CFN Enterprises Inc. (OTCQB: CNFN), owner and operator of CFN Media, the industry’s leading agency and digital financial media network dedicated to the burgeoning CBD and legal cannabis industries. Call +1 (833) 420-CNFN for more information.

About Ryan Allway

Mr. Allway has over a decade of experience in the financial markets as both a private investor and financial journalist. He has been actively involved in the cannabis industry since its inception, covering public and private companies.

• Unlocking the potential of psychedelics, including DMT, and other tryptamines to treat the significant unmet medical needs of glaucoma patients
• Partnering with world-renowned research institution brings validated drug delivery expertise in novel, controlled drug-release technologies

Toronto, Ontario–(Newsfile Corp. – August 5, 2021) – PharmaDrug Inc. (CSE: PHRX) (OTC Pink: LMLLF) (“PharmaDrug” or the “Company“), a specialty pharmaceutical company focused on the research, development and commercialization of controlled-substances and natural medicines such as psychedelics, cannabis and naturally-derived approved drugs, is pleased to announce that PharmaDrug has entered into a sponsored research agreement with the Terasaki Institute to develop a novel ocular drug delivery platform that aims to deliver psychedelic and tryptamine-based pharmaceuticals, such as N, N-dimethyltryptamine (“DMT”), for eye diseases.

PharmaDrug will focus on developing a novel ocular drug delivery platform to deliver DMT and other undisclosed tryptamines as a potential therapeutic solution in treating the significant unmet medical needs of glaucoma patients. Glaucoma is a disorder of the optic nerve that results in irreversible vision loss and is the second leading cause of blindness in the world, according to the World Health Organization. Glaucoma impacts more than 2.7 million people aged 40 or older in the United States and current treatments are known to have poor rates of compliance of up to 80% of patients. The global market for glaucoma was estimated by Market Scope at $4.8 billion in 2019 with the U.S. market representing $1.9 billion.

Although the exact etiology of primary open angle glaucoma remains poorly understood, and may be variable across patient subsets, it is generally accepted that the observed increase in intraocular pressure (IOP) correlates with progressive vision loss¹. As such, currently available glaucoma treatments, most commonly formulated into eye drops, are designed to lower IOP. While these approaches provide partial improvement, they often result in side effects such as redness and stinging and require multiple daily applications; all of which diminish patient compliance.

Key regions of the eye that regulate fluid dynamics, including maintenance of healthy IOP, are known to be richly decorated with various serotonin receptor family members. Previous research has highlighted the role of serotonin receptor signaling in the regulation of IOP^2-5. Tryptamines, often hallucinogenic above certain threshold concentrations, constitute a large collection of molecules that selectively act on multiple different serotonin receptors including 5-HT1A and 5-HT2A. Topical application of several different tryptamines have shown early promise in preclinical models of elevated IOP, however formulation, delivery, the potential for undesirable hallucinogenic side effects, and the controlled substances act of 1970 have all contributed to a lack of development of tryptamines to treat this serious threat to vision. PharmaDrug, working with the renowned Terasaki Research Institute, has entered into a sponsored research agreement that will evaluate multiple candidate tryptamines, including DMT in various preclinical models of glaucoma. Studies will include cell-based basic research, active pharmaceutical ingredient formulation, and exploitation of novel delivery technologies aimed at improving patient outcome by delivering the optimal drug in a convenient format that improves compliance and diminishes side effects.

The Terasaki Institute for Biomedical Innovation is a biotechnology institute which develops medical devices and cutting-edge protocols for a variety of diagnostic, monitoring and treatment applications. Their research platforms include work in biomaterials, cellular and tissue engineering, wearable biosensors and organs-on-a-chip, with specific expertise in novel polymer development.

“We are very excited to partner with the Terasaki Institute, a leader in the design and development of novel drug delivery technologies. This relationship will expedite our development plan and move us meaningfully closer to our goal of evaluating DMT and other tryptamines for various types of eye disease which require both a pharmacological and delivery solution to fill the significant treatment gap in glaucoma,” said Daniel Cohen, Chairman and CEO of PharmaDrug. “By aligning ourselves with thought leaders in the space we aim to tackle the worthy challenge of developing a novel delivery device that will provide sub-psychedelic quantities of candidate tryptamines to the front of the eye.”

Dr. Ali Khademhosseini, CEO of the Terasaki Institute commented: “At the Terasaki Institute we have a number of core competences in developing next generation medical technologies such as polymer-based formulations and wearables for drug delivery purposes. We have partnered with various pharmaceutical and biotechnology companies seeking to evolve their product offerings in treating significant unmet medical needs. PharmaDrug’s unique proposed solution to the challenges that are present in eye diseases is what motivates the Terasaki team to answer the call in developing a drug delivery system that would positively affect the millions of people who suffer with impaired vision and compromised quality of life. We are excited to be working with PharmaDrug and be a part of their journey in their quest to develop therapeutic solutions for eye disease.”

About PharmaDrug Inc.

PharmaDrug is a specialty pharmaceutical company focused on the research, development and commercialization of controlled-substances and natural medicines such as psychedelics, cannabis and naturally-derived approved drugs. The Company owns 80% of Pharmadrug Production GmbH, a German medical cannabis distributor, with a Schedule I European Union narcotics license and German EuGMP certification allowing for the importation and distribution of medical cannabis to pharmacies in Germany and throughout the EU. The Company also owns 100% of Super Smart, a Dutch company building a modern adult use psychedelic retail business with an elevated and educational focus. PharmaDrug recently acquired Sairiyo Therapeutics, a biotech company that specializes in researching and reformulating established natural medicines with a goal of bringing them through regulatory and research driven clinical trials.

For further information, please contact:

Daniel Cohen, Chairman and CEO
[email protected]
(647) 202-1824

Caution Regarding Forward-Looking Information:

THE CANADIAN SECURITIES EXCHANGE HAS NOT REVIEWED NOR DOES IT ACCEPT RESPONSIBILITY FOR THE ADEQUACY OR ACCURACY OF THIS RELEASE.

This news release may contain forward-looking statements and information based on current expectations. These statements should not be read as guarantees of future performance or results of the Company. Such statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by such statements. Although such statements are based on management’s reasonable assumptions, there can be no assurance that such assumptions will prove to be correct. We assume no responsibility to update or revise them to reflect new events or circumstances. The Company’s securities have not been registered under the U.S. Securities Act of 1933, as amended (the “U.S. Securities Act”), or applicable state securities laws, and may not be offered or sold to, or for the account or benefit of, persons in the United States or “U.S. Persons”, as such term is defined in Regulations under the U.S. Securities Act, absent registration or an applicable exemption from such registration requirements. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the securities in the United States or any jurisdiction in which such offer, solicitation or sale would be unlawful. Additionally, there are known and unknown risk factors which could cause the Company’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking information contained herein, such as, but not limited to dependence on obtaining regulatory approvals; the ability to locate additional supply of medical cannabis, owning interests in companies or projects that are engaged in activities currently considered illegal under United States federal law; changes in laws; limited operating history, reliance on management, requirements for additional financing, competition, hindering market growth; regulatory and political change. All forward-looking information herein is qualified in its entirety by this cautionary statement, and the Company disclaims any obligation to revise or update any such forward-looking information or to publicly announce the result of any revisions to any of the forward-looking information contained herein to reflect future results, events or developments, except as required by law.

Forward-looking information is subject to known and unknown risks, uncertainties and other factors that may cause the actual results, level of activity, performance or achievements of the Company to be materially different from those expressed or implied by such forward-looking information. Such risks and other factors may include, but are not limited to: general business, economic, competitive, political and social uncertainties; general capital market conditions and market prices for securities; the actual results of the Company’s future operations; competition; changes in legislation affecting the Company; the ability to obtain and maintain required permits and approvals, the timing and availability of external financing on acceptable terms; lack of qualified, skilled labour or loss of key individuals; risks related to the COVID-19 pandemic including various recommendations, orders and measures of governmental authorities to try to limit the pandemic, including travel restrictions, border closures, non-essential business closures, service disruptions, quarantines, self-isolations, shelters-in-place and social distancing, disruptions to markets, economic activity, financing, supply chains and sales channels, and a deterioration of general economic conditions; and a deterioration of financial markets that could limit the Company’s ability to obtain external financing.

A description of additional risk factors that may cause actual results to differ materially from forward-looking information can be found in the Company’s disclosure documents on the SEDAR website at www.sedar.com. Although the Company has attempted to identify important factors that could cause actual results to differ materially from those contained in forward-looking information, there may be other factors that cause results not to be as anticipated, estimated or intended. Accordingly, readers should not place undue reliance on forward-looking information. Readers are cautioned that the foregoing list of factors is not exhaustive. Readers are further cautioned not to place undue reliance on forward-looking information as there can be no assurance that the plans, intentions or expectations upon which they are placed will occur. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated.

The Company’s securities have not been registered under the U.S. Securities Act of 1933, as amended (the “U.S. Securities Act”), or applicable state securities laws, and may not be offered or sold to, or for the account or benefit of, persons in the United States or “U.S. Persons”, as such term is defined in Regulations under the U.S. Securities Act, absent registration or an applicable exemption from such registration requirements. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the securities in the United States or any jurisdiction in which such offer, solicitation or sale would be unlawful.

Forward-looking information contained in this press release is expressly qualified by this cautionary statement. The forward-looking information contained in this press release represents the expectations of the Company as of the date of this press release and, accordingly, are subject to change after such date. However, the Company expressly disclaims any intention or obligation to update or revise any forward-looking information, whether as a result of new information, future events or otherwise, except as expressly required by applicable securities law.

References:

1. Weinreb RN, Leung CK, Crowston JG, Medeiros FA, Friedman DS, Wiggs JL, Martin KR. Primary open-angle glaucoma. Nat Rev Dis Primers. 2016 Sep 22;2:16067. doi: 10.1038/nrdp.2016.67. PMID: 27654570.
2. May JA, McLaughlin MA, Sharif NA, Hellberg MR, Dean TR. Evaluation of the ocular hypotensive response of serotonin 5-HT1A and 5-HT2 receptor ligands in conscious ocular hypertensive cynomolgus monkeys. J Pharmacol Exp Ther. 2003 Jul;306(1):301-9. doi: 10.1124/jpet.103.049528. Epub 2003 Apr 3. PMID: 12676887.
3. Sharif NA. Serotonin-2 receptor agonists as novel ocular hypotensive agents and their cellular and molecular mechanisms of action. Curr Drug Targets. 2010 Aug;11(8):978-93. doi: 10.2174/138945010791591278. PMID: 20426763.
4. Najam A Sharif & Jesse A May (2011) Potential for serotonergic agents to treat elevated intraocular pressure and glaucoma: focus on 5-HT2 receptor agonists, Expert Review of Ophthalmology, 6:1, 105-120, DOI: 10.1586/eop.10.69
5. Sharif NA, McLaughlin MA, Kelly CR. AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist. J Ocul Pharmacol Ther. 2007 Feb;23(1):1-13. doi: 10.1089/jop.2006.0093. PMID: 17341144.

This article was published by CFN Enterprises Inc. (OTCQB: CNFN), owner and operator of CFN Media, the industry’s leading agency and digital financial media network dedicated to the burgeoning CBD and legal cannabis industries. Call +1 (833) 420-CNFN for more information.

• THCVHS combined with netarsudil (Rhopressa®) achieves an average maximum intraocular pressure (IOP) reduction of 32.4% and maintains an average IOP reduction of 26.5% at 9 hours, significantly better than any single drug or combination tested
• THCVHS demonstrates superior IOP-lowering and duration relative to glaucoma standard of care, latanoprost

San Diego, Calif, May 17, 2021 (GLOBE NEWSWIRE) — Skye Bioscience, Inc. (OTCQB: SKYE) (“SKYE” or the “Company”), a biopharmaceutical company developing proprietary, synthetic cannabinoid-derived molecules to treat glaucoma and other diseases with significant unmet need, announced that in a preclinical study assessing intraocular pressure (IOP)-lowering effects of its novel prodrug, THCVHS combined with netarsudil demonstrated the most significant IOP-lowering effects and duration of activity compared to all other tested single and combined treatments. Data from this study also highlighted THCVHS’ superior IOP-lowering capability and duration of activity as a single agent compared to the current standard of care for the treatment of glaucoma, latanoprost.

Elevated IOP is a key risk factor in the progression of glaucoma and the result of fluid build-up in the anterior compartment of the eye. Although current therapies attempt to lower IOP by decreasing fluid production or increasing fluid drainage, many patients respond poorly to specific drugs, build tolerance, or do not experience sufficient lowering of IOP to slow disease progression. More than half of patients eventually require two or more drugs to adequately control their IOP. This leaves a significant need and opportunity for new drugs and classes of therapies, especially ones that increase the magnitude and duration of therapeutic effects.

Previous studies conducted with the University of Mississippi (UM) established that THCVHS decreased IOP significantly and over a longer duration than the top two commercially available treatments, latanoprost and timolol. Clinical evidence suggests that combining different classes of IOP-lowering drugs can provide additional benefit for some patients. This new study was designed, in collaboration with UM, to determine the benefit of combining THCVHS with other classes of IOP-lowering drugs, specifically a prostaglandin analogue (latanoprost) and a rho kinase inhibitor (netarsudil).

This study demonstrated that THCVHS combined with netarsudil achieved superior IOP-lowering and durability compared to latanoprost. Latanoprost’s average maximum IOP-lowering effect was 21.3% and it returned to baseline after 9 hours; THCVHS combined with netarsudil achieved an average maximum IOP-lowering effect of 32.4% and retained an average reduction in IPO of 26.5% at 9 hours. The data also showed superior IOP-lowering compared to netarsudil combined with latanoprost.

This study also reaffirmed THCVHS’ superior ability to significantly lower IOP over a longer duration compared to latanoprost: THCVHS achieved an average maximum reduction in IOP of 27.5% and maintained an average reduction in IOP of 21.1% after 9 hours, at which point latanoprost had returned to baseline.

“Our group has had significant experience formulating THCVHS for a variety of therapeutic indications and continues to discover new therapeutic applications for this promising molecule,” said Soumyajit Majumdar, PhD, Professor, Department of Pharmaceutics and Drug Delivery at University of Mississippi. “This study again highlights THCVHS’ superiority as a single agent over latanoprost to lower intraocular pressure, including its ability to maintain a significant therapeutic effect beyond nine hours. Importantly, the data also suggests the potential to further enhance the intraocular-pressure-lowering capabilities of THCVHS by combining it with specific alternative classes of IOP-lowering drugs. We anticipate sharing the complete set of data as part of a manuscript to be submitted to a peer-reviewed academic journal.”

“This new study provides positive new observations regarding THCVHS’ potential to provide advantageous therapeutic benefits for patients, both as a single agent and combined with other drugs, and we plan to fully investigate these possibilities,” said Punit Dhillon, Skye Bioscience, CEO. “These data suggest there is strong potential for THCVHS to be a once-a-day treatment, a desirable outcome for glaucoma treatments. With our recently announced progression on manufacturing and imminent toxicology studies, we continue our progress toward our first-in-human trial for THCVHS that is intended to start later this year.”

Study design

This study was conducted in collaboration with the University of Mississippi using three in vivo groups. Each group received a single 50 µL dose of THCVHS, latanoprost or netarsudil once daily for the first five days and then a combination of two different drugs once daily for the next five days. In the combined drug study, the second drug was administered 15 minutes after administering the first drug. IOP was measured over the course of 24 hours on days 1, 3 and 5 using single drug treatment and days 6, 8 and 10 using combination drug treatment. The study was performed with the following treatment regimens:

Single Drug Regimens

• Group 1: THCVHS 1.0%
• Group 2: latanoprost 0.005%
• Group 3: netarsudil 0.02%

Combined Drug Regimens

• Group 1: THCVHS 1.0% followed by netarsudil 0.02%
• Group 2: latanoprost 0.005% followed by THCVHS 1.0%
• Group 3: netarsudil 0.02% followed by latanoprost 0.005%

About THCVHS
THCVHS, a proprietary prodrug of tetrahydrocannabinol (THC), is a topical ocular formulation under development to treat glaucoma. Developed with rational drug design and biochemical engineering, THCVHS is a proprietary synthetic molecule that enables local delivery of the drug into the eye and reduces the potential for systemic side effects. In preclinical studies, THCVHS demonstrated superior lowering of intraocular pressure, a major risk factor related to irreversible vision loss, compared to the standard-of-care glaucoma treatment.

About the University of Mississippi
The University of Mississippi, the state’s flagship institution, is among the elite group of R-1: Doctoral Universities – Highest Research Activity in the Carnegie Classification. The university has a long history of producing leaders in public service, academics, research, and business. Its 15 academic divisions include a major medical school, nationally recognized schools of accountancy, law and pharmacy, and an Honors College acclaimed for a blend of academic rigor, experiential learning, and opportunities for community action.

UM’s research interests include studies of the botanical, pharmacological and chemical properties of the cannabis plant. Since 1968, the marijuana research lab at University of Mississippi’s School of Pharmacy has been the only facility in the United States permitted by the federal government’s National Institute on Drug Abuse to cultivate cannabis for research purposes.

About Skye Bioscience
Skye Bioscience Inc. is a biopharmaceutical company unlocking the pharmaceutical potential of cannabinoids through the development of its proprietary, cannabinoid-derived molecules to treat diseases with significant unmet needs. The company’s lead program, THCVHS, is focused on treating glaucoma, a disease with no cure and the world’s leading cause of irreversible blindness. For more information, please visit: www.skyebioscience.com.

CONTACT
Karam Takhar
VP, Corporate Development & Investor Relations
Email: [email protected]
Phone: (858) 410-0266

FORWARD LOOKING STATEMENTS

This press release contains forward-looking statements, including statements regarding our product development, business strategy, timing of clinical trials and commercialization of cannabinoid-derived therapeutics. Such statements and other statements in this press release that are not descriptions of historical facts are forward-looking statements that are based on management’s current expectations and assumptions and are subject to risks and uncertainties. If such risks or uncertainties materialize or such assumptions prove incorrect, our business, operating results, financial condition, and stock price could be materially negatively affected. In some cases, forward-looking statements can be identified by terminology including “anticipated,” “plans,” “goal,” “focus,” “aims,” “intends,” “believes,” “can,” “could,” “challenge,” “predictable,” “will,” “would,” “may” or the negative of these terms or other comparable terminology. We operate in a rapidly changing environment and new risks emerge from time to time. As a result, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements the Company may make. Risks and uncertainties that may cause actual results to differ materially include, among others, our capital resources, uncertainty regarding the results of future testing and development efforts and other risks that are described in the Risk Factors section of Skye’s most recent annual or quarterly report filed with the Securities and Exchange Commission. Except as expressly required by law, Skye disclaims any intent or obligation to update these forward-looking statements.

This article was published by CFN Enterprises Inc. (OTCQB: CNFN), owner and operator of CFN Media, the industry’s leading agency and digital financial media network dedicated to the burgeoning CBD and legal cannabis industries. Call +1 (833) 420-CNFN for more information.

About Ryan Allway

Mr. Allway has over a decade of experience in the financial markets as both a private investor and financial journalist. He has been actively involved in the cannabis industry since its inception, covering public and private companies.