Curaleaf International to Present Positive Clinical and Pre-Clincial Research

Clinical study demonstrates significant improvement in pain

Curaleaf International (the "Company") part of Curaleaf Holdings (CNSX:CURA), Europe's largest vertically integrated cannabis company, is pleased to announce that Chief Scientific Officer, Dr Barbara Pacchetti will present research on one clinical study and three preclinical studies at a leading conference on medical cannabis on 21-22 October 2022. These papers have been peer-reviewed and selected for presentation and publication in the official Conference Proceedings Journal Medical Cannabis and Cannabinoids (Karger Publishers, Basel, Switzerland).

Research to be presented from the clinical study focuses on the delivery of a cannabidiol (CBD) preparation to patients with Vestibulodynia (VBD) which is a prevalent form of chronic genital pain in women with no standard treatment. The study, a randomized placebo control study, of 60 patients showed significant improvement of outcomes on pain, dyspareunia (genital pain before, during or after sex), pelvic muscular tone and neurometer parameters, which highlights implications for its anti-inflammatory, anti-nociceptive action and anti-neuropathic therapeutic potential. The title of the paper is: Transmucosal delivery of cannabidiol using vestibular electroporation in patients with vestibulodynia: interim analysis of a randomized, blinded prospective trial. The co-authors are F. Murina, Prof. MD., F. Vicariotto, Prof. MD and Barbara Pacchetti, Chief Scientific Officer at Curaleaf International.

Preclinical research to be presented focuses on the potential positive impact of CBD on the treatment of several psychiatric disorders and inflammatory disease, the therapeutic potential for migraine pain and trigeminal excitability related to migraine. For further information on the preclinical research to be presented, please see the footnote at the end of this announcement. *

Dr. Barbara Pacchetti, Chief Scientific Officer at Curaleaf International, commented, "We are very pleased with the findings from our clinical study on the delivery of CBD to treat patients with VBD, and that it is showing a significant improvement in pain outcomes for patients. Additionally, the preclinical research on the therapeutic potential of CBD to treat a number of other indications is also encouraging and I look forward to presenting this to the scientific community and to furthering our research into the potential for CBD. We believe the growth and understanding of medical cannabis must be underpinned by the most robust science. Curaleaf International is working with some of the world's leading academic institutions such as Imperial College, the University of Milan and University of Insubria and we look forward to further updating all stakeholders with our progress."

To learn more about the conference please visit the conference website .

About Curaleaf International
Curaleaf International (formerly EMMAC Life Sciences Group) is Europe's largest vertically integrated cannabis company, bringing together pioneering science and research with cutting-edge cultivation, extraction and production. With a unique supply and distribution network throughout Europe, Curaleaf International's vision is to bring the life-enhancing potential of cannabis to the people who need it. EMMAC Life Sciences was acquired by Curaleaf Holdings in March 2021.

For more information about Curaleaf International, please visit:
https://www.curaleafinternational.com/

About Curaleaf Holdings
Curaleaf Holdings, Inc. (CSE: CURA) (OTCQX: CURLF) ("Curaleaf") is a leading international provider of consumer products in cannabis with a mission to improve lives by providing clarity around cannabis and confidence around consumption. As a high-growth cannabis company known for quality, expertise and reliability, the Company and its brands, including Curaleaf, Select, and Grassroots provide industry-leading service, product selection and accessibility across the medical and adult-use markets. In the United States, Curaleaf currently operates in 21 states with 144 dispensaries, 26 cultivation sites, and employs over 6,000 team members. Curaleaf International is the largest vertically integrated cannabis company in Europe with a unique supply and distribution network throughout the European market, bringing together pioneering science and research with cutting-edge cultivation, extraction and production. Curaleaf is listed on the Canadian Securities Exchange under the symbol CURA and trades on the OTCQX market under the symbol CURLF. For more information, please visit https://ir.curaleaf.com .

*Details on the preclinical studies
Cannabidiol (CBD) is considered a valuable potential treatment for several psychiatric disorders. This preclinical study demonstrates, for the first time, that CBD is detected in the plasma and medial prefrontal cortex (mPFC), following single or repeated treatment at therapeutical doses, with a specific dose-response profile. CBD significantly modulates brain-derived neurotrophic factor (BDNF) expression, a neurotrophin critical for synaptic plasticity, following a brain specific anatomical pattern. This modulatory effect on BDNF might be functionally relevant and represent added value for the potential therapeutic role of CBD in psychiatric disorders.

(Title and Authors: Cannabidiol exposure modulated the BDNF system in the rat cortico-striatal circuitry – F. Mottarlini, M. Fumagalli, F. Castillo-Diaz, S. Piazza, G. Targa, E. Sangiovanni, B. Pacchetti, M.H. Sodergren, M. Dell'Agli, F. Fumagalli and L. Caffino)

Polymorphonuclear leukocytes (PMN) are the first immune cell to be recruited into inflammatory sites, and cannabidiol (CBD) extensively affects their functions. This study confirmed the anti-inflammatory activity of CBD on some PMN functions observed in a previous study. Results indicate that CBD counteracts the effects of priming on key functions such as migration and ROS production, strengthening its therapeutic potential in inflammatory disease.

(Title and Authors: Effects of cannabidiol on migration and reactive oxygen species production in bacterial lipopolysaccharide primed human polymorphonuclear leukocyte - F. Marino, E. Rasini, A. Luini, M. Legnaro, A. Gemma, B. Pacchetti, M. H. Sodergren, M. Cosentino)

Clinical and preclinical data have suggested a deregulation of the endocannabinoid system (ECS) in migraine pain and trigeminal excitability related to migraine. This in-vivo study evaluated and found key information on the accumulation of Cannabidiol (CBD) in brain areas that are involved in migraine pain in an animal model at therapeutical doses chronically, and evidenced that a single CBD administration may reduce trigeminal hyperalgesia in an animal model for migraine pain. The results suggested the capability of CBD to modulate migraine-related nociceptive transmission via specific central and peripheral regions.

(Title and Authors: Cannabidiol as a potential treatment for migraine: preliminary data in an animal model. R Greco, C Demartini, M Francavilla, M Palmisani, A M Zanaboni, R Marchiselli, S Facchetti, V Franco, B Pacchetti, C Tassorelli)

CAUTIONARY STATEMENT
All statements, other than statements of historical fact, in this news release are forward-looking statements that involve various risks and uncertainties, including, without limitation, statements regarding potential values, the future plans and objectives of Curaleaf International. There can be no assurance that such statements will prove to be accurate, achievable or recognisable in the near term.

Actual results and future events could differ materially from those anticipated in such statements. These and all subsequent written and oral forward-looking statements are based on the estimates and opinions of management on the dates they are made and are expressly qualified in their entirety by this notice. Curaleaf International assumes no obligation to update forward-looking statements should circumstances or management's estimates or opinions change.

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