I-Neuroimaging, i-Cannabis, nokusebenza kweBongo nokusebenza

"Ngicabanga ukuthi imbiza kufanele ibe semthethweni. Angiyibhemi, kodwa ngithanda iphunga layo." —U-Andy Warhol

I-Cannabis iqukethe ama-molecule ahlukahlukene abopha ama-receptors ebuchosheni, abizwa ngokufanele ngokuthi "ama-cannabinoid receptors." Ama-ligands ajwayelekile (abophezela kulawo ma-receptors) afaka i-THC (tetrahydrocannabinol) ne-CBD (i-cannabidiol), ebopha kuma-receptors afana ne-CB1 ne-CB2 receptors anemisebenzi ehlukahlukene esezansi ebuchosheni.

I-neurotransmitter eyinhloko ebandakanyeka emisebenzini ye-cannabinoid ye-innate (endo native) ye-cannabinoid "i-anandamide," "i-fatty acid neurotransmitter" ehlukile egama layo lisho ukuthi "injabulo," "injabulo," noma "injabulo" ngesiSanskrit nezilimi zasendulo ezihlobene. Lolu hlelo lwe-neurotransmitter lusanda kuphenywa ngokuningiliziwe, futhi i-biology eyisisekelo isetshenzwe kahle (isb., Kovacovic & Somanathan, 2014), kuthuthukiswa ukuqonda ngemiphumela yokwelapha, yokuzijabulisa, nemiphumela emibi yama-cannabinoid ahlukahlukene, nokuvula indlela yokuthuthukiswa kwezidakamizwa zokwenziwa kwenoveli.

Intshisekelo ekhulayo ekusetshenzisweni kokwelashwa nokuzijabulisa kwensangu idinga ukuqonda okukhulu ngemiphumela yensangu ebuchosheni nasekuziphatheni. Ngenxa yensangu ephikisanayo nepolitiki enkulumweni yomphakathi, izinkolelo eziqinile mayelana nensangu zivimba amandla ethu okuba nezingxoxo ezinengqondo mayelana nobuhle nobubi bokusetshenziswa kwensangu futhi zivimbele izinhlelo zocwaningo. Yize kunjalo, izifundazwe eziningi zivumele ukusetshenziswa kwezokwelapha nokuzilibazisa kwamalungiselelo e-cannabis, ngenkathi uhulumeni wesifundazwe ebuyela emuva ebheka ezinkambisweni ezivimbela kakhulu.

Abasizi bejaji baphumile

Abameli be-cannabis, ngakolunye uhlangothi, bangaveza isithombe esihle kakhulu sezinzuzo zamalungiselelo e-cannabis, behlise phansi noma balahle imininingwane efanelekile mayelana nobungozi be-cannabis kubantu abathile abasengozini yokuphazamiseka okuthile kwengqondo, ubungozi bokuphazamiseka kokusebenzisa insangu, kanye imiphumela emibi ye-cannabis ezinkambisweni ezithile zokuqonda ezihambisana nemiphumela engahle ibe yingozi, futhi ibe yingozi, ekuthathweni kwezinqumo nasekuziphatheni.

Isibonelo, ngenkathi amalungiselelo e-cannabis ekhonjisiwe ukuthi alusizo ekuphathweni kobuhlungu nasekuthuthukisweni kokusebenza ezimweni ezahlukahlukene, ukwenza ngcono impilo, i-cannabis nayo ingadala amaphutha ekwahluleleni nasekubambezelweni kokucutshungulwa kolwazi, okungaholela ezinkingeni zomuntu ngamunye, kepha ingangena endleleni yobudlelwano nemisebenzi yobungcweti, ize iholele ekulimaleni kwabanye ngokunikela ezingozini.

I-Cannabis ihlotshaniswe ngokusobala nokwenza ukuthi ezinye izifo ziqale futhi zibe zimbi kakhulu, ikakhulukazi izimo zengqondo. Ngaphezu kwalokho, kunentshisekelo ekhulayo yokuqonda amandla okwelapha nawokugula ezinhlanganisela ezahlukahlukene eziqukethwe ngaphakathi kwamalungiselelo e-cannabis, ikakhulukazi i-THC ne-CBD-yize ukubaluleka kwezinye izinto kuya ngokuya kuqashelwa. Isibonelo, ucwaningo lwakamuva ku I-American Journal of Psychiatry luphakamisa ngokuqinile ukuthi i-CBD, ewusizo ekwelapheni ukuquleka okungangeneki (isib. I-Rosenberg et al., 2015), ingaba usizo olukhulu njenge-ejenti yokwengeza yabathile abane-schizophrenia (McGuire at al ., 2017).

Isithombe asikho-noma, noma kunjalo. Ukuqonda okujule kakhulu kokuthi i-cannabis izithinta kanjani izifunda ezahlukahlukene zobuchopho (ngaphansi kwezimo ezahlukahlukene, isib. futhi unikeze okutholakele okuqinile, nokwethembekile kwesayensi ukuvula indlela yocwaningo lwesikhathi esizayo. Ukuqonda okuyisisekelo kuyashoda, kanti ngenkathi kunomkhakha ocwaningayo owandayo obheka izici ezahlukahlukene zemiphumela ye-cannabis, njengoba kuhlala kwenzeka ngomzimba ocwaningayo oguqukayo ekuqaleni, indlela iye yahlukahluka ezifundweni eziningi ezincane, ngaphandle kohlaka olucacile khuthaza izindlela ezingaguquguquki zokuphenya.

Umbuzo owodwa obaluleke ngokusobala uthi: Iyini imiphumela ye-cannabis ezindaweni ezibalulekile zokusebenza kobuchopho? Ngabe ukusebenza nokuxhuma kushintsha kanjani ngaphakathi kwezifunda ezibalulekile ze-anatomic (“hubs,” kumqondo wenethiwekhi) zisakazeka kanjani kumanethiwekhi wobuchopho aphakathi kwawo? Isebenzisa kanjani i-cannabis, lapho siqonda khona imiphumela yayo, edlala ngaphakathi kwemisebenzi ethile esetshenziselwa ukutadisha ukuqonda? Ngokuvamile, yini umphumela wensangu kumanethiwekhi obuchopho, kufaka phakathi imodi yokuzenzakalelayo, ukulawula okuphezulu, kanye namanethiwekhi we-salience (amanethiwekhi amathathu abalulekile ku- "club ecebile" exhunywe kakhulu yamanethiwekhi wobuchopho)?

Le mibuzo kanye neminye ehlobene nayo ibaluleke kakhulu njengoba siqonda kangcono ukuthi igebe lengqondo / lobuchopho lingavalwa kanjani yinqubekela phambili yokwenza ibalazwe i-neural connectome yomuntu. Ukulindela ukuthi ukukhuphuka noma ukwehla kokusebenza ezindaweni ezahlukahlukene zobuchopho kubasebenzisi (uma kuqhathaniswa nabangewona abasebenzisi) kuzohambisana nezinguquko ezibanzi kumanethiwekhi wobuchopho asebenzayo, akhonjiswa emaphethini wokusebenza okuhlukile eqenjini elikhulu lamathuluzi wokucwaninga ngokwengqondo asetshenziswa kakhulu ezithwebula izici ezahlukahlukene zokusebenza kwengqondo nokuziphatha komuntu.

Ucwaningo lwamanje

Ngalokhu kucatshangelwa okubalulekile emqondweni, iqembu labacwaningi abaningi (u-Yanes et al., 2018) laqala ukuqoqa futhi lihlole yonke imibhalo efanele ye-neuroimaging ebheka imiphumela ye-cannabis ebuchosheni nasekuziphatheni nasekusebenzeni kwengqondo.

Kuyafaneleka ukubukeza indlela ye-meta-analytic esetshenziswe kafushane nokuxoxa ngezinhlobo zezinhlobo zezifundo ezifakiwe nezakhishelwa ngaphandle, ukuze kubekwe esimeni kanye nokuhumusha okutholakele okubaluleke kakhulu. Babheka izincwadi ezibandakanya izifundo ezisebenzisa i-fMRI (imaging resonance imaging esebenzayo) kanye nezikena ze-PET (positron emission tomography), amathuluzi ajwayelekile wokukala izinkomba zomsebenzi wobuchopho, futhi benza ukuhlolwa kokuqala kokuhlela idatha.

Okokuqala, bahlukanisa izifundo zaba lapho okwenziwa khona umsebenzi ezindaweni ezahlukahlukene zobuchopho noma kwehliswa kubasebenzisi kuqhathaniswa nabangewona abasebenzisi futhi kwaqondaniswa nezindawo ze-anatomic namanethiwekhi asebenzayo obuchopho ayingxenye yazo. Kusendlalelo sesibili sokucwengwa, basebenzise "ukusombulula okusebenzayo" ukukhomba nokuhlukanisa amaqembu ahlukene wemisebenzi yezengqondo elinganiswa kuyo yonke imibhalo ekhona.

Isibonelo, ucwaningo lubheka isethi enkulu kepha ehlukahlukene yemisebenzi yezengqondo ukubona ukuthi, uma kunjalo, i-cannabis iguqula kanjani ukucubungula kwengqondo nokucabanga ngokomzwelo. Imisebenzi efanele ifaka phakathi ukuthatha izinqumo, ukutholwa kwephutha, ukulawulwa kokungqubuzana, ukuthinta umthethonqubo, umvuzo nemisebenzi yokugqugquzela, ukulawula umfutho, imisebenzi ephezulu, nenkumbulo, ukuhlinzeka ngohlu olungaphelele. Ngoba izifundo ezahlukahlukene zisebenzise ukuhlolwa okwehlukile ngaphansi kwezimo ezahlukahlukene, ukuthuthukisa indlela yokuhlaziya ehlanganisiwe kuyadingeka ukwenza ukubuyekeza okuphelele nokuhlaziya.

Isesha imininingwane eminingi ejwayelekile, bakhethe izifundo ezinokuqhathanisa abasebenzisi nabangewona abasebenzisi, nedatha etholakala ngendlela yamamodeli ajwayelekile afanele ukuhlaziywa okuhlanganisiwe, futhi okubandakanya ukuhlolwa kwengqondo kokuqonda, ukunyakaza, imizwa, ukucabanga, kanye nokulungiswa kwemininingwane yezenhlalo, inhlanganisela ehlukahlukene. Bakhiphe ngaphandle labo abanezimo zempilo yengqondo, kanye nezifundo ezibheke imiphumela esheshayo yokusetshenziswa kwensangu. Bahlaziye le datha ekhethiwe.

Uma sibheka ukuhlangana kokutholakele kwe-neuroimaging ezifundweni zonke kusetshenziswa i-ALE (Activation Likelihood Estimate, eguqula idatha iye kumodeli ejwayelekile yokwenza imephu yobuchopho), bathole ukuthi iziphi izifunda ebezingasebenzi kangako. Kusetshenziswa i-MACM (Meta-Analytic Connectivity Modeling, esebenzisa i-BrainMap database ukwenza amakhompiyutha wokusebenza kobuchopho bonke), bakhomba amaqoqo ezifunda zobuchopho ezasebenza ndawonye.

Baqedile isigaba sokusebenza sokumiswa ngokubheka phambili futhi babuyekeze amaphethini we-inference ukuxhumanisa ngokusobala umsebenzi wobuchopho nokusebenza kwengqondo, nokusebenza kwengqondo nomsebenzi wobuchopho, ukuqonda ukuthi izinqubo ezahlukahlukene zengqondo zihlangana kanjani nemisebenzi ezifundeni ezahlukahlukene zobuchopho.

Nasi isifinyezo se-meta-analytic "pipeline" ephelele:

Okutholakele

UYanes, Riedel, Ray, Kirkland, Bird, Boeving, Reid, Gonazlez, Robinson, Laird, and Sutherland (2018) bahlaziye izifundo ezingama-35. Konke kukhulunyiwe, kunezimo ezingama-88 ezisuselwa emisebenzini, nezinto ezingama-202 ezihlobene nokwehla kokusebenza phakathi kwabasebenzisi be-cannabis abangama-472 kanye nabangasebenzisi i-466, kanye nezinto ze-161 maqondana nokwanda kokusebenzisa phakathi kwabasebenzisi be-482 kanye nabangasebenzisi i-434. Kwakunezindawo ezintathu ezinkulu zokutholakele:

Kube nezindawo eziningana zezinguquko ezingaguquguquki ("eziguquguqukayo") eziqashelwe phakathi kwabasebenzisi nabangewona abasebenzisi, maqondana nokwenza kusebenze nokungasebenzi. Ukwehla kubonwe emazweni womabili (zombili izinhlangothi zobuchopho) i-ACCs (anterior cingulate cortex) kanye ne-DLPFC yangakwesokudla (dorsolateral prefrontal cortex). Ngokuphambene, kwakukhona ukusebenza okwandisiwe okubonwa ngokungaguquguquki ku-striatum elungile (futhi kudlulela endaweni efanele). Kubalulekile ukuqaphela ukuthi lokhu okutholakele bekuhlukile komunye nomunye, futhi lokhu kushoda kokugqagqana kusho ukuthi imele imiphumela ehlukile yensangu ezinhlelweni ezahlukahlukene.

Ukuhlaziywa kwe-MACM kukhombisile ukuthi kukhona amaqoqo amathathu ezifunda zobuchopho ezisebenzisanayo:

• ICluster 1 - I-ACC ifake amaphethini wokwenza konke ukusebenza kobuchopho, kufaka phakathi ukuxhumana ne-insular ne-caudate cortex, i-medial frontal cortex, i-precuneus, i-fusiform gyrus, i-culmen, i-thalamus ne-cingate cortex. I-ACC iyisihluthulelo sokwenza izinqumo nokulungisa ukungqubuzana futhi iyabandakanyeka ekuhloleni nasekuzinikeleni enkambweni enikeziwe (isb., Kolling et al., 2016), futhi lezi zindawo ezihlobene zimboza imisebenzi ebanzi ehlobene ne-ACC. I-insula ibandakanyeka ekuzibukeni ngokwakho, isibonelo esiphawuleka ngokuba yisipiliyoni se-visceral sokuzenyanya.
• ICluster 2 - I-DLPFC ifake ukusebenza ngokubambisana nezifunda zeparietal, i-orbitofrontal cortex, i-occipital cortex, ne-fusiform gyrus. Njengoba i-DLPFC ibandakanyeka emisebenzini ebalulekile yokuphatha, kufaka phakathi ukulawula imizwa, ulwazi lwenhliziyo, kanye nokuqondiswa kwezinsizakusebenza (isib. UMondino kwa-al., 2015) kanye nezici zokucutshungulwa kolimi, nezindawo ezihlobene nazo zibhekisa imisebenzi ebalulekile, kufaka phakathi ukucutshungulwa kolwazi lomphakathi, ukulawula umfutho, nokuhlobene.
• ICluster 3 - iStriatum ifake ukubandakanyeka kobuchopho bonke, ikakhulukazi i-insular cortex, i-cortex engaphambili, i-parietal lobule ephezulu, i-fusiform gyrus, nama-culmen. I-striatum ibandakanyeka emvuzweni — lokho okubizwa nge- “dopamine hit” okukhulunywa ngakho kaningi — okuthi lapho kulawulwa kahle kusivumele siphishekele impumelelo enkulu, kepha ezifundeni zokungasebenzi kahle kuholela ekungenzi lutho, futhi ngokweqile kunomthelela ekuziphatheni okuluthayo nasekucindezelweni . Ubufakazi obubuyekezwe ephepheni lakuqala bukhombisa ukuthi ukusetshenziswa kwensangu kungahle kube yimiklomelo eyinhloko yokuthola ukuluthwa, kanye nokugqugquzela okungenamqondo kwemisebenzi ejwayelekile.

Ngenkathi la maqoqo ehluke ngokusebenza ngokuthi athinteka kanjani yi-cannabis, ahlangana ngokwedlulele nangokwendawo, aqokomisa ukubaluleka okubalulekile kokusebenza kobuchopho okubukwayo kusuka ku-connectome, endaweni exhunyanisiwe ukuze kuqondwe ukuhunyushwa kokutholwa kobuchopho obunciphisayo ukuthi kanjani ingqondo isebenza, nokuthi lokhu kudlala kanjani kubantu empilweni yansuku zonke.

Ukuchazwa kokusebenza kwamaqoqo amathathu kukhombisa amaphethini wokuthi iqoqo ngalinye lihlangana kanjani neqembu lokuhlolwa kwengqondo: isibonelo, ukuhlolwa kweStroop, go / no-go okubandakanya izinqumo ezisheshayo, imisebenzi yokuqapha ubuhlungu, nemisebenzi yokuhlola umvuzo, ukuze yisho okumbalwa. Ngeke ngizibuyekeze zonke, kepha okutholakele kufanelekile, futhi okunye kwakho kugqamile (bheka ngezansi).

Lokhu kubuka konke kobudlelwano beqoqo lomsebenzi kuyasiza. Okuqapheleka kakhulu ubukhona besimo somsebenzi wokuhamba / ukungahambi kuzo zontathu izindawo ezisebenzayo:

Ukucatshangelwa okuqhubekayo

Sekuhlanganiswe ndawonye, ​​imiphumela yalokhu kuhlaziywa kwemeta inkulu futhi ifinyelela ezinhlosweni zokugxila ekutholeni nasekuhluzeni okutholakele ezincwadini ezifanele eziphenya ngemiphumela yokusetshenziswa kwe-cannabis ekusebenzeni kobuchopho kubantu ngaphandle kokugula kwengqondo, kubhekwa imisebenzi eyandisiwe nenciphisiwe izifunda zobuchopho, amaqoqo asatshalaliswa okubaluleka okuhlukile, kanye nomthelela emisebenzini ebalulekile yokusebenza kwengqondo nokusebenza.

I-Cannabis yehlisa umsebenzi kuwo womabili amaqoqo e-ACC ne-DLPFC, nakubantu abasebenza ngokujwayelekile kobuchopho, lokhu kungaholela ezinkingeni ekusebenzeni okuphezulu nasekwenzeni izinqumo. Insangu kungenzeka idale ukunganemba ekuqapheni amaphutha, okuholele ekuqondeni kabi nasezindabeni zokusebenza ngenxa yamaphutha, futhi kungaphazamisa ukusebenza ngesikhathi sezimo ezinokushayisana okukhulu, kusukela emaphutheni womabili ekwahluleleni nasekuthathweni kwezinqumo nasekubulaweni okwalandela. Ukwehla komsebenzi we-DLPFC kungaholela ezinkingeni zokulawulwa ngokomzwelo, kanye nokwehla kwememori nokunciphisa ukulawula ukunakwa.

Kubantu abanezimo zengqondo nezokwelapha, imiphumela efanayo yobuchopho ingaba ekwelapheni, ngokwesibonelo ukunciphisa umthwalo wezinhlungu ngokunciphisa umsebenzi we-ACC, ukunciphisa izinkumbulo ezihlukumezayo nokucindezela amaphupho amabi ngemuva kokuhlukumezeka, ukwelapha ukukhathazeka ngemiphumela emibi embalwa, noma ukunciphisa izimpawu zengqondo (McGuire, 2017) ngokuvimbela umsebenzi ezindaweni ezithintekayo zobuchopho.

Kepha ama-cannabinoids nawo angadala i-pathology, aqede ukucindezeleka noma i-psychosis, nezinye izimo, kubantu abasengozini. Ukusetshenziswa kwe-cannabis kubangela nezinkinga zobuchopho obukhulayo, okuholela emiphumeleni engathandeki yesikhathi eside (isb., UJacobus noTappert, 2014), njengokunciphisa ukusebenza kwe-neurocognitive kanye nezinguquko zesakhiwo ebuchosheni.

I-cannabis ikhonjisiwe, ngokuhlukile, ukwandisa umsebenzi ku-striatum nezindawo ezihlobene ngokuvamile. Kubantu abanomsebenzi ojwayelekile oyisisekelo, lokhu kungaholela ekukhulisweni kwamasekethe emivuzo, futhi njengoba sekubonwe ezifundweni eziningi, kungakhuphula ubungozi bokuziphatha okuluthayo nokuphoqelelayo, okubeka ezinye izinhlobo zezifo. Lokhu kukhuliswa komsebenzi womvuzo (kuhlanganiswe nemiphumela emaqoqweni amabili okuqala) kungaba nomthelela "ekuphuzeni" kakhulu kokudakwa kwensangu, kuthuthukisa ukujabula nomsebenzi wobuciko, okwenza yonke into ibe namandla kakhulu futhi ihlanganyele, okwesikhashana.

Ababhali baqaphela ukuthi womathathu amaqoqo abandakanyeka emsebenzini wokuhamba / ukungahambi, isimo sokuhlola esidinga ukuvinjelwa noma ukusebenza kwesenzo sezimoto. Bayaphawula:

"Lapha, iqiniso lokuthi ukuphazanyiswa okuqondene nesifunda esithile kuxhunyaniswe nokwenziwa komsebenzi ofanayo kungahle kube yinkomba yomphumela ohlobene nensangu obonakala ezifundweni zonke. Ngamanye amagama, amandla anciphile okuvimbela isimilo esinenkinga angaxhunyaniswa nokwehliswa okufanayo umsebenzi wangaphambi kokuqalwa (i-ACC ne-DL-PFC) nokuphakanyiswa komsebenzi wokubulala. "

Kwezinye iziguli, insangu kubikwa ukuthi inciphisa izimpawu zokudangala, ezibonakala ngokuhlangenwe nakho okuyinhloko kokulahlekelwa yinjabulo, izimo ezingokomzwelo ezeqile ngokweqile, kanye nokuntuleka kwesisusa, phakathi kwezinye izimpawu, kepha abasebenzisi abasindayo basengozini enkulu yokwanda kokucindezeleka (UManrique-Garcia et al ., 2012).

Kodwa-ke, ngokungezelela ekunciphiseni ukulutha kwamanye amakhemikhali nokuthuthukisa amava kulabo abathanda ukudakwa yinsangu (abanye bakuthola kukhiqiza i-dysphoria, ukukhathazeka, ukudideka okungathandeki, noma i-paranoia), abasebenzisi bangathola ukuthi lapho kungekho ukusetshenziswa kwensangu , abanandaba kangako nemisebenzi ejwayelekile lapho ingekho phezulu, okuholela ekunciphiseni ukujabula kanye nogqozi.

Le miphumela yehlukile ngokuya ngezici eziningana ezihlobene nokusetshenziswa kwe-cannabis, njengesikhathi nesikhathi sokusetshenziswa okungapheli, kanye nohlobo lwe-cannabis kanye ne-chemistry ehambisanayo, enikezwe ukuhlukahluka phakathi kwezinhlobo ezahlukahlukene nezinhlobo. Ngenkathi lolu cwaningo lungakwazanga ukuhlukanisa phakathi kwemiphumela ye-THC ne-CBD, njengoba idatha ibingatholakali ekugxileni noma ekulinganisweni kwalezi zinto ezimbili ezibalulekile ku-cannabis, kungenzeka ukuthi zinemiphumela ehlukile ekusebenzeni kobuchopho okudinga ukuqhubeka kophenyo ukuze kuhlungwe amandla okwelashwa avela emiphumeleni yokuzijabulisa neyokugula.

Lolu cwaningo luyisisekelo sesisekelo, lubeka isiteji sokucwaninga okuqhubekayo ngemiphumela yama-cannabinoid ahlukahlukene ebuchosheni kwezempilo nasekuguleni, nokunikeza imininingwane ebalulekile ukuqonda imiphumela yokwelapha neyingozi yama-cannabinoid ahlukahlukene. Indlela ebabazekayo nenesizotha kulolu cwaningo icacisa ukuthi i-cannabis ibuthinta kanjani ubuchopho, inikeze ngemininingwane ebalulekile ngemiphumela isiyonke kumanethiwekhi obuchopho nasekusebenzeni kwengqondo nasemqondweni.

Imibuzo enentshisekelo ifaka phakathi ukwenziwa kwemephu yamanethiwekhi obuchopho nokuhlobanisa lokhu okutholakele namamodeli akhona engqondo, ukubheka umphumela wezinhlobo ezahlukahlukene zensangu namaphethini wokusetshenziswa, nokuphenya umphumela wama-cannabinoids (okwenzeka ngokwemvelo, okokugcina, nokwenziwa ) ngezinhloso zokwelashwa ezimeni ezahlukahlukene zomtholampilo, ukusetshenziswa kokuzijabulisa, futhi okungenzeka kube nokwenza ngcono ukusebenza.

Okokugcina, ngokunikeza uhlaka oluhambisanayo lokuqonda izincwadi ezikhona ezibandakanya imiphumela emihle nemibi ye-cannabis ebuchosheni, leli phepha ligxila ocwaningweni lwe-cannabis ngokusobala kakhulu esifundweni sesayensi, sihlinzeka ngeplatifomu engathathi hlangothi, enenhlamba yokuvumela impikiswano ku-cannabis ukuze iguquke ngezikhombisi ezakhayo ngokwengeziwe kunangaphambili.

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