Anti-Obesity Drug Discovery and Development

Volume: 5

Harnessing Addiction Neuroscience to Treat Obesity

Author(s): Diana Sketriene, Sarah S. Ch’ng and Robyn M. Brown * .

Pp: 66-123 (58)

DOI: 10.2174/9789811423178121050005

* (Excluding Mailing and Handling)

Abstract

The prevalence and impact of obesity are staggering. It has reached pandemic proportions, over a third of the global population is overweight or obese (40 million are children). With >2.8 million deaths/year attributable to overweight/obesity, it is now the 5th leading cause of global deaths and is rapidly surpassing smoking as the number one killer in the industrialized world. Exciting pharmacotherapies for treatment of obesity showed only modest success in clinical trials and the most effective treatment, bariatric surgery, is reserved for selected patients and associated with risks of morbidity and mortality. Thus, the frontline treatment for obesity remains the promotion of lifestyle changes, which mainly relies on permanent changes in diet. Unfortunately, most people find it challenging to maintain calories deficit and eat less caloric food. Thereby it is crucial to understand why people overeat and why it is so difficult to resist the urge to eat “junk food” even in the absence of hunger. A growing body of research has identified striking similarities between attributes of addiction and pathological overeating. Imagery studies showed that stimuli associated with food or drugs and craving for them activate the same brain regions. As with drugs of abuse, overeating may be used as a method of self-medication in response to negative emotional states, such as depression, anxiety, loneliness, boredom and interpersonal conflict. Notably, an overlap exists in medication that influences intake of both food and drugs of abuse (e.g. topiramate, naltrexone). Moreover, human and animal studies have shown similar changes in neurochemistry (e.g. dopamine, endogenous opioids), synaptic plasticity (e.g. nucleus accumbens) and behaviour (e.g. increased impulsivity, compulsive intake, cognitive impairments) in obese and drug addicted subjects. This emerging evidence supports the hypothesis that the brain’s reward circuitry may be dysregulated in case of obesity. Therefore, we propose that the incorporation of addiction neuroscience into the conceptualization and treatment of pathological overeating has the potential to improve treatment outcomes. This chapter will review potential drug targets for treatment of excessive eating in obesity within an addiction neuroscience framework.


Keywords: Addiction, Behaviour, Drugs of abuse, High-fat high-sugar, Highly palatable, Obesity, Overeating, Reward-based eating.

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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309824417 and j.to_ip >=309824417 )) and ((j.from_date <= 1740472392 and j.to_date >= 1740472392 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14693) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309824417 and j.to_ip >=309824417 )) and ((j.from_date <= 1740472392 and j.to_date >= 1740472392 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14693) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309824417 and j.to_ip >=309824417 )) and ((j.from_date <= 1740472392 and j.to_date >= 1740472392 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14693)
      1.06msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 2885 and `b`.`banner_from_date` <= 1740472392 and `b`.`banner_to_date` >= 1740472392 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.6msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2885
      • 3: 1740472392
      • 4: 1740472392
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='e1b44bb9fec8e77cb3301b6af7f7e29c'
      350μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    8Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        Ug2nvoixo6B5kkfydDAETwqUgg1ytWZX8Nxl4vkp
        uc_cart_id
        e1b44bb9fec8e77cb3301b6af7f7e29c
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/14693" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/14693
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IkswRFdtcEs2ZGhkSHRjZzFId2ptTVE9PSIsInZhbHVlIjoiZTlDa3FWRDNDRnB6OU1LN2pWQURuLzFVTUdmTzZ5QmFCdlJlRkVYZzB4VT0iLCJtYWMiOiJjZmQ3YjhiNmRlMGRkNzUwYTMzNjJlZDUzNDM3MDI1YzAyMGVkOGM3OGVhOTM3OTA0MjE5OGZlNzc5ZjJhMjY5IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IkswRFdtcEs2ZGhkSHRjZzFId2ptTVE9PSIsInZhbHVlIjoiZTlDa3FWRDNDRnB6OU1LN2pWQURuLzFVTUdmTzZ5QmFCdlJlRkVYZzB4VT0iLCJtYWMiOiJjZmQ3YjhiNmRlMGRk" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 08:33:12 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkR4MHRhbGtOMWQxbFR5dWdmNFNaZ1E9PSIsInZhbHVlIjoiTHQrYlJQZ0hhQVFWWjJ1ejEzL2JFNkdQZDRWV01mZ0o1UkN2Q003Njd1cnQ2QjJleEdETEFDYmt1N1BjQy9kWWpXSnM0Q1RRdEM5dEp3QmlCaFhjbVBmck9sdlMvTDZxTU9TbGNDcWd1dXNEdzlxWXpUVCtnc3hhdDJRWEhFYVciLCJtYWMiOiJlZWEwZWU1NjgzNzVkODkwOWFkODYyZDZlZTM2YzdhNzM3MmRjNWE5Mzk3MmVjMjFjN2M5MmJhNzcxMzgxMTRkIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 20:33:12 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkR4MHRhbGtOMWQxbFR5dWdmNFNaZ1E9PSIsInZhbHVlIjoiTHQrYlJQZ0hhQVFWWjJ1ejEzL2JFNkdQZDRWV01mZ0o1UkN2Q003Njd1cnQ2QjJleEdETEFDYmt1N1BjQy9kWWpXSnM0Q" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImFBYVJGQWhCN0thSGlBTkJkT3FHWmc9PSIsInZhbHVlIjoiaE42bEc3N1RvTENNem9haGlpdDV3cGQ0OVpLYUpKaEZlTjQramVIUmF4SDlIbE0zWm1YdDlnQkIzazFBMlF0RUo0enkvQVBDOHUyUHErZXRIWU9uaVJTajN4WUNLRENEbjhkR1lwM2NOTjFpZSt0LysvRHQ5Tmg3cUNHZU5xbkciLCJtYWMiOiJhOTY3YzgxOTE5OTRmMDEyY2RjNmY4ZjExNzRjY2U0N2QwODFmM2MwMzk1ODZlOTFkNTcwZDBiYmI4MGM1MTcyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImFBYVJGQWhCN0thSGlBTkJkT3FHWmc9PSIsInZhbHVlIjoiaE42bEc3N1RvTENNem9haGlpdDV3cGQ0OVpLYUpKaEZlTjQramVIUmF4SDlIbE0zWm1YdDlnQkI" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkR4MHRhbGtOMWQxbFR5dWdmNFNaZ1E9PSIsInZhbHVlIjoiTHQrYlJQZ0hhQVFWWjJ1ejEzL2JFNkdQZDRWV01mZ0o1UkN2Q003Njd1cnQ2QjJleEdETEFDYmt1N1BjQy9kWWpXSnM0Q1RRdEM5dEp3QmlCaFhjbVBmck9sdlMvTDZxTU9TbGNDcWd1dXNEdzlxWXpUVCtnc3hhdDJRWEhFYVciLCJtYWMiOiJlZWEwZWU1NjgzNzVkODkwOWFkODYyZDZlZTM2YzdhNzM3MmRjNWE5Mzk3MmVjMjFjN2M5MmJhNzcxMzgxMTRkIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 20:33:12 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkR4MHRhbGtOMWQxbFR5dWdmNFNaZ1E9PSIsInZhbHVlIjoiTHQrYlJQZ0hhQVFWWjJ1ejEzL2JFNkdQZDRWV01mZ0o1UkN2Q003Njd1cnQ2QjJleEdETEFDYmt1N1BjQy9kWWpXSnM0Q" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImFBYVJGQWhCN0thSGlBTkJkT3FHWmc9PSIsInZhbHVlIjoiaE42bEc3N1RvTENNem9haGlpdDV3cGQ0OVpLYUpKaEZlTjQramVIUmF4SDlIbE0zWm1YdDlnQkIzazFBMlF0RUo0enkvQVBDOHUyUHErZXRIWU9uaVJTajN4WUNLRENEbjhkR1lwM2NOTjFpZSt0LysvRHQ5Tmg3cUNHZU5xbkciLCJtYWMiOiJhOTY3YzgxOTE5OTRmMDEyY2RjNmY4ZjExNzRjY2U0N2QwODFmM2MwMzk1ODZlOTFkNTcwZDBiYmI4MGM1MTcyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImFBYVJGQWhCN0thSGlBTkJkT3FHWmc9PSIsInZhbHVlIjoiaE42bEc3N1RvTENNem9haGlpdDV3cGQ0OVpLYUpKaEZlTjQramVIUmF4SDlIbE0zWm1YdDlnQkI" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "Ug2nvoixo6B5kkfydDAETwqUgg1ytWZX8Nxl4vkp" "uc_cart_id" => "e1b44bb9fec8e77cb3301b6af7f7e29c" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/14693" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 08:33:12GET/chapter/146931121910